TOP2A

Summary

Gene Symbol: TOP2A
Description: DNA topoisomerase II alpha
Alias: TOP2, TP2A, DNA topoisomerase 2-alpha, DNA gyrase, DNA topoisomerase (ATP-hydrolyzing), DNA topoisomerase II, 170 kD, DNA topoisomerase II, alpha isozyme, topoisomerase (DNA) II alpha 170kDa
Species: human
Products:     TOP2A

Top Publications

  1. Villman K, Sjöström J, Heikkilä R, Hultborn R, Malmström P, Bengtsson N, et al. TOP2A and HER2 gene amplification as predictors of response to anthracycline treatment in breast cancer. Acta Oncol. 2006;45:590-6 pubmed
    The purpose of this study was to evaluate amplification of topoisomerase IIalpha (TOP2A) and HER2 genes as predictors of response to chemotherapy in advanced breast cancer...
  2. Luo K, Yuan J, Chen J, Lou Z. Topoisomerase IIalpha controls the decatenation checkpoint. Nat Cell Biol. 2009;11:204-10 pubmed publisher
    ..Mutation of Ser 1524 results in a defective decatenation checkpoint. These results reveal an important role of Topo II in checkpoint activation and in the maintenance of genomic stability. ..
  3. Lazaris A, Kavantzas N, Zorzos H, Tsavaris N, Davaris P. Markers of drug resistance in relapsing colon cancer. J Cancer Res Clin Oncol. 2002;128:114-8 pubmed
    ..Therapeutic options after failure of 5-fluorouracil-based treatment could therefore include appropriate topoisomerase IIalpha-targeted drugs. ..
  4. Sakaguchi A, Kikuchi A. Functional compatibility between isoform alpha and beta of type II DNA topoisomerase. J Cell Sci. 2004;117:1047-54 pubmed
    ..Double-knockdown experiments also revealed that topo II was required for shortening of the chromosome axis. ..
  5. Sabo E, Meitner P, Tavares R, Corless C, Lauwers G, Moss S, et al. Expression analysis of Barrett's esophagus-associated high-grade dysplasia in laser capture microdissected archival tissue. Clin Cancer Res. 2008;14:6440-8 pubmed publisher
    ..The genes identified include several previously implicated in the pathogenesis of BE-associated dysplasia and new candidates for further investigation. ..
  6. Gogou P, Batistatou A, Pakos E, Apostolikas N, Stefanou D, Tsekeris P. Expression of E-cadherin, beta-catenin and topoisomerase IIalpha in leiomyosarcomas. Clin Transl Oncol. 2009;11:548-51 pubmed
    ..From the analysed factors, tumour size was statistically significantly correlated with relapse-free survival. Further evidence with larger series is required in order to determine the implication of these markers in LMS. ..
  7. Kroll D, Sullivan D, Gutierrez Hartmann A, Hoeffler J. Modification of DNA topoisomerase II activity via direct interactions with the cyclic adenosine-3',5'-monophosphate response element-binding protein and related transcription factors. Mol Endocrinol. 1993;7:305-18 pubmed
  8. Wray J, Williamson E, Royce M, Shaheen M, Beck B, Lee S, et al. Metnase mediates resistance to topoisomerase II inhibitors in breast cancer cells. PLoS ONE. 2009;4:e5323 pubmed publisher
    ..Metnase could also become an important target for combination chemotherapy with current Topo IIalpha inhibitors, specifically in anthracycline-resistant breast cancer. ..
  9. Karnes R, Cheville J, Ida C, Sebo T, Nair A, Tang H, et al. The ability of biomarkers to predict systemic progression in men with high-risk prostate cancer treated surgically is dependent on ERG status. Cancer Res. 2010;70:8994-9002 pubmed publisher
    The objective of this study was to assess the relationship of the tumor protein levels of TOP2A and MIB-1 and ERG status with cancer-specific outcomes in men with high-risk prostate cancer treated by radical prostatectomy (RP)...

More Information

Publications102 found, 100 shown here

  1. Lou Z, Minter Dykhouse K, Chen J. BRCA1 participates in DNA decatenation. Nat Struct Mol Biol. 2005;12:589-93 pubmed
    ..Together these results suggest an important role of BRCA1 in DNA decatenation and reveal a previously unknown function of BRCA1 in the maintenance of genomic stability. ..
  2. Alchanati I, Teicher C, Cohen G, Shemesh V, Barr H, Nakache P, et al. The E3 ubiquitin-ligase Bmi1/Ring1A controls the proteasomal degradation of Top2alpha cleavage complex - a potentially new drug target. PLoS ONE. 2009;4:e8104 pubmed publisher
    ..Top1, Top2alpha and Top2beta are important molecular targets for antitumor drugs, which specifically poison Top1 or Top2 isomers...
  3. Press M, Sauter G, Buyse M, Bernstein L, Guzman R, Santiago A, et al. Alteration of topoisomerase II-alpha gene in human breast cancer: association with responsiveness to anthracycline-based chemotherapy. J Clin Oncol. 2011;29:859-67 pubmed publisher
    Approximately 35% of HER2-amplified breast cancers have coamplification of the topoisomerase II-alpha (TOP2A) gene encoding an enzyme that is a major target of anthracyclines...
  4. Knoop A, Knudsen H, Balslev E, Rasmussen B, Overgaard J, Nielsen K, et al. retrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: . J Clin Oncol. 2005;23:7483-90 pubmed
    The aim of the study was to evaluate the predictive value of HER2 and topoisomerase IIalpha gene (TOP2A) for the efficacy of epirubicin in the adjuvant setting of breast cancer patients...
  5. Washiro M, Ohtsuka M, Kimura F, Shimizu H, Yoshidome H, Sugimoto T, et al. Upregulation of topoisomerase IIalpha expression in advanced gallbladder carcinoma: a potential chemotherapeutic target. J Cancer Res Clin Oncol. 2008;134:793-801 pubmed publisher
    ..Etoposide induced apoptosis of OCUG-1 cells. TOPO IIalpha might be an effective chemotherapeutic target in advanced gallbladder carcinoma, especially when it is expressed strongly. ..
  6. Williamson E, Rasila K, Corwin L, Wray J, Beck B, Severns V, et al. The SET and transposase domain protein Metnase enhances chromosome decatenation: regulation by automethylation. Nucleic Acids Res. 2008;36:5822-31 pubmed publisher
    ..Thus, Metnase enhances Topo IIalpha decatenation, and this activity is repressed by automethylation. These results suggest that cancer cells could subvert Metnase to mediate clinically relevant resistance to Topo IIalpha inhibitors. ..
  7. Chikamori K, Grabowski D, Kinter M, Willard B, Yadav S, Aebersold R, et al. Phosphorylation of serine 1106 in the catalytic domain of topoisomerase II alpha regulates enzymatic activity and drug sensitivity. J Biol Chem. 2003;278:12696-702 pubmed
    ..These results demonstrate that Ca(2+)-regulated phosphorylation of Ser-1106 in the catalytic domain of topo II alpha modulates the enzymatic activity of this protein and sensitivity to topo II-targeting drugs. ..
  8. Järvinen T, Liu E. Topoisomerase IIalpha gene (TOP2A) amplification and deletion in cancer--more common than anticipated. Cytopathology. 2003;14:309-13 pubmed
    ..other biologically relevant genes with altered copy numbers, among these genes is the topoisomerase IIalpha (TOP2A)...
  9. Carpenter A, Porter A. Construction, characterization, and complementation of a conditional-lethal DNA topoisomerase IIalpha mutant human cell line. Mol Biol Cell. 2004;15:5700-11 pubmed
  10. Kondapi A, Padmaja G, Satyanarayana N, Mukhopadyaya R, Reitz M. A biochemical analysis of topoisomerase II alpha and beta kinase activity found in HIV-1 infected cells and virus. Arch Biochem Biophys. 2005;441:41-55 pubmed
    ..The catalytic inhibitions by serine kinase inhibitors further suggest that the alpha and beta kinase activities associated with virus are distinctly different. ..
  11. Tsai Pflugfelder M, Liu L, Liu A, Tewey K, Whang Peng J, Knutsen T, et al. Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22. Proc Natl Acad Sci U S A. 1988;85:7177-81 pubmed
    ..II gene were determined from these and several additional clones, identified through the use of the cloned human TOP2 gene sequences as probes...
  12. Cowell I, Okorokov A, Cutts S, Padget K, Bell M, Milner J, et al. Human topoisomerase IIalpha and IIbeta interact with the C-terminal region of p53. Exp Cell Res. 2000;255:86-94 pubmed
    ..Furthermore, we show that the regulatory C-terminal basic region of p53 (residues 364-393) is necessary and sufficient for interaction with DNA topo II. ..
  13. Bhargava R, Lal P, Chen B. HER-2/neu and topoisomerase IIa gene amplification and protein expression in invasive breast carcinomas: chromogenic in situ hybridization and immunohistochemical analyses. Am J Clin Pathol. 2005;123:889-95 pubmed
    ..Identification of topo2a and HER-2 status might have therapeutic and prognostic implications. ..
  14. Linka R, Porter A, Volkov A, Mielke C, Boege F, Christensen M. C-terminal regions of topoisomerase IIalpha and IIbeta determine isoform-specific functioning of the enzymes in vivo. Nucleic Acids Res. 2007;35:3810-22 pubmed
    ..Our results show that it is the CTRs of human topoisomerase II that determine their isoform-specific functions in proliferating cells. They also indicate persistence of some functional redundancy between the two isoforms. ..
  15. Jonstrup A, Thomsen T, Wang Y, Knudsen B, Koch J, Andersen A. Hairpin structures formed by alpha satellite DNA of human centromeres are cleaved by human topoisomerase IIalpha. Nucleic Acids Res. 2008;36:6165-74 pubmed publisher
    ..Based on this a model is discussed, where topoisomerase II interacts with two hairpins as a mediator of centromere cohesion. ..
  16. Stros M, Bacikova A, Polanská E, Stokrova J, Strauss F. HMGB1 interacts with human topoisomerase IIalpha and stimulates its catalytic activity. Nucleic Acids Res. 2007;35:5001-13 pubmed
    ..The observed abilities of HMGB1 to interact with topo IIalpha and promote topo IIalpha binding to DNA suggest a mechanism by which HMGB1 stimulates the catalytic activity of the enzyme via enhancement of DNA cleavage. ..
  17. Wendorff T, Schmidt B, Heslop P, Austin C, Berger J. The structure of DNA-bound human topoisomerase II alpha: conformational mechanisms for coordinating inter-subunit interactions with DNA cleavage. J Mol Biol. 2012;424:109-24 pubmed publisher
    ..9-Å-resolution structure of the DNA cleavage core of human topoisomerase II? (TOP2A) bound to a doubly nicked, 30-bp duplex oligonucleotide...
  18. Bromberg K, Osheroff N. DNA cleavage and religation by human topoisomerase II alpha at high temperature. Biochemistry. 2001;40:8410-8 pubmed
    ..Finally, similar high-temperature alterations were observed for yeast topoisomerase II and human topoisomerase IIbeta, suggesting that parallel heat-induced transitions may be widespread among type II topoisomerases. ..
  19. Tubbs R, Barlow W, Budd G, Swain E, Porter P, Gown A, et al. Outcome of patients with early-stage breast cancer treated with doxorubicin-based adjuvant chemotherapy as a function of HER2 and TOP2A status. J Clin Oncol. 2009;27:3881-6 pubmed publisher
    Amplification and deletion of the TOP2A gene have been reported as positive predictive markers of response to anthracycline-based therapy...
  20. Escargueil A, Plisov S, Filhol O, Cochet C, Larsen A. Mitotic phosphorylation of DNA topoisomerase II alpha by protein kinase CK2 creates the MPM-2 phosphoepitope on Ser-1469. J Biol Chem. 2000;275:34710-8 pubmed
    ..In conclusion, we have identified protein kinase CK2 as a new MPM-2 kinase able to phosphorylate an important mitotic protein, topoisomerase II alpha, on Ser-1469. ..
  21. Liu D, Huang C, Kameyama K, Hayashi E, Yamauchi A, Sumitomo S, et al. Topoisomerase IIalpha gene expression is regulated by the p53 tumor suppressor gene in nonsmall cell lung carcinoma patients. Cancer. 2002;94:2239-47 pubmed
    ..0224). The current study suggests that Topo IIalpha gene expression is regulated by p53 gene status in NSCLC patients and that the overexpression of Topo IIalpha induced by mutant p53 might cause more aggressive carcinogenesis. ..
  22. Usha L, Tabesh B, Morrison L, Rao R, Jacobson K, Zhu A, et al. Topoisomerase II alpha gene copy loss has adverse prognostic significance in ERBB2-amplified breast cancer: a retrospective study of paraffin-embedded tumor specimens and medical charts. J Hematol Oncol. 2008;1:12 pubmed publisher
    ..In approximately 25% of these patients, the amplicon extends to the gene for topoisomerase II alpha (TOP2A), a target for anthracyclines...
  23. Romero A, Martin M, Cheang M, López García Asenjo J, Oliva B, He X, et al. Assessment of Topoisomerase II ? status in breast cancer by quantitative PCR, gene expression microarrays, immunohistochemistry, and fluorescence in situ hybridization. Am J Pathol. 2011;178:1453-60 pubmed publisher
    Anthracyclines are frequently used for the treatment of breast cancer and topoisomerase II alpha (TOP2A) is considered to be the molecular target...
  24. Di Leo A, Desmedt C, Bartlett J, Piette F, Ejlertsen B, Pritchard K, et al. HER2 and TOP2A as predictive markers for anthracycline-containing chemotherapy regimens as adjuvant treatment of breast cancer: a meta-analysis of individual patient data. Lancet Oncol. 2011;12:1134-42 pubmed publisher
    ..We aimed to assess the value of HER2 and TOP2A as predictive markers of response to anthracycline-based adjuvant therapy in patients with early breast cancer...
  25. Johnson C, Padget K, Austin C, Turner B. Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis. J Biol Chem. 2001;276:4539-42 pubmed
    ..We suggest that chromatin remodeling by an HDAC-containing complex facilitates both topo II-catalyzed DNA rearrangement and etoposide-induced DNA damage in vivo. ..
  26. Christensen M, Larsen M, Barthelmes H, Hock R, Andersen C, Kjeldsen E, et al. Dynamics of human DNA topoisomerases IIalpha and IIbeta in living cells. J Cell Biol. 2002;157:31-44 pubmed
    ..These observations suggest that topo II is not an immobile, structural component of the chromosomal scaffold or the interphase karyoskeleton, but rather a dynamic interaction partner of such structures. ..
  27. Albadine R, Wang W, Brownlee N, Toubaji A, Billis A, Argani P, et al. Topoisomerase II alpha status in renal medullary carcinoma: immuno-expression and gene copy alterations of a potential target of therapy. J Urol. 2009;182:735-40 pubmed publisher
  28. Wells N, Addison C, Fry A, Ganapathi R, Hickson I. Serine 1524 is a major site of phosphorylation on human topoisomerase II alpha protein in vivo and is a substrate for casein kinase II in vitro. J Biol Chem. 1994;269:29746-51 pubmed
    ..Site-directed mutagenesis studies identified these casein kinase II-specific phosphorylation sites as serine 1524 and serine 1376. ..
  29. Nikolényi A, Sukosd F, Kaizer L, Csörgo E, Voros A, Uhercsak G, et al. Tumor topoisomerase II alpha status and response to anthracycline-based neoadjuvant chemotherapy in breast cancer. Oncology. 2011;80:269-77 pubmed publisher
    ..Anthracyclines target the enzyme topoisomerase II? (TOP2A)...
  30. Wells N, Hickson I. Human topoisomerase II alpha is phosphorylated in a cell-cycle phase-dependent manner by a proline-directed kinase. Eur J Biochem. 1995;231:491-7 pubmed
    ..Our data implicate one or more proline-directed kinases in the cell-cycle-dependent regulation of topoisomerase II alpha enzyme activity in human cells. ..
  31. Corzo C, Bellosillo B, Corominas J, Salido M, Coll M, Serrano S, et al. Does polysomy of chromosome 17 have a role in ERBB2 and topoisomerase IIalpha expression? Gene, mRNA and protein expression: a comprehensive analysis. Tumour Biol. 2007;28:221-8 pubmed
    ..Our results demonstrate that polysomy of chromosome 17 is not related to ERBB2 expression. Thereby, it is important to use centromeric probes to clearly discriminate between true ERBB2 gene amplification and polysomy of chromosome 17. ..
  32. Simon R, Atefy R, Wagner U, Forster T, Fijan A, Bruderer J, et al. HER-2 and TOP2A coamplification in urinary bladder cancer. Int J Cancer. 2003;107:764-72 pubmed
    ..In breast cancer, the adjacent TOP2A gene, the molecular target for several anticancer drugs, is frequently coamplified together with HER-2...
  33. Shinagawa H, Miki Y, Yoshida K. BRCA1-mediated ubiquitination inhibits topoisomerase II alpha activity in response to oxidative stress. Antioxid Redox Signal. 2008;10:939-49 pubmed
    ..We conclude that the functions of topoisomerase IIalpha are regulated by ubiquitination on exposure to oxidative stress. ..
  34. Faggad A, Darb Esfahani S, Wirtz R, Sinn B, Sehouli J, Könsgen D, et al. Topoisomerase IIalpha mRNA and protein expression in ovarian carcinoma: correlation with clinicopathological factors and prognosis. Mod Pathol. 2009;22:579-88 pubmed publisher
    ..Our results encourage the further evaluation of the prognostic and predictive values of Top IIalpha expression in ovarian carcinoma, which might help to assess the patients' risk profile, and the planning of an individualized therapy. ..
  35. Hasby E, Saied E. Immunohistochemical expression of topoisomerase II alpha and Her-2/neu in prostatic carcinoma and benign prostatic hyperplasia. J Egypt Natl Canc Inst. 2008;20:158-67 pubmed
    ..The latter finding may have important therapeutic implications, however, further large scale studies are required for confirmation. Topo II a - Her-2/neu - Prostatic carcinoma - BPH. ..
  36. Malhotra S, Lapointe J, Salari K, Higgins J, Ferrari M, Montgomery K, et al. A tri-marker proliferation index predicts biochemical recurrence after surgery for prostate cancer. PLoS ONE. 2011;6:e20293 pubmed publisher
    ..We assayed three proliferation signature genes: MKI67 (Ki-67; also a classic proliferation biomarker), TOP2A (DNA topoisomerase II, alpha), and E2F1 (E2F transcription factor 1)...
  37. Watt P, Hickson I. Structure and function of type II DNA topoisomerases. Biochem J. 1994;303 ( Pt 3):681-95 pubmed
  38. Shapiro P, Whalen A, Tolwinski N, Wilsbacher J, Froelich Ammon S, Garcia M, et al. Extracellular signal-regulated kinase activates topoisomerase IIalpha through a mechanism independent of phosphorylation. Mol Cell Biol. 1999;19:3551-60 pubmed
  39. Bjergbaek L, Jensen S, Westergaard O, Andersen A. Using a biochemical approach to identify the primary dimerization regions in human DNA topoisomerase IIalpha. J Biol Chem. 1999;274:26529-36 pubmed
    ..The result indicates that secondary interactions occur by ATP analog-mediated clamp closing when the subunits are brought together on DNA. ..
  40. Mirski S, Bielawski J, Cole S. Identification of functional nuclear export sequences in human topoisomerase IIalpha and beta. Biochem Biophys Res Commun. 2003;306:905-11 pubmed
    ..Our results provide the first evidence of active nuclear export of topoisomerase II and suggest it is mediated by a CRM1-dependent pathway. ..
  41. Mielke C, Christensen M, Barthelmes H, Boege F. Enhanced processing of UVA-irradiated DNA by human topoisomerase II in living cells. J Biol Chem. 2004;279:20559-62 pubmed
  42. Yun J, Tomida A, Andoh T, Tsuruo T. Interaction between glucose-regulated destruction domain of DNA topoisomerase IIalpha and MPN domain of Jab1/CSN5. J Biol Chem. 2004;279:31296-303 pubmed
    ..These findings demonstrate that GRDD can act as a stress-activated degron for regulating topo IIalpha stability, possibly through interaction with the MPN domain of Jab1/CSN5. ..
  43. McClendon A, Rodriguez A, Osheroff N. Human topoisomerase IIalpha rapidly relaxes positively supercoiled DNA: implications for enzyme action ahead of replication forks. J Biol Chem. 2005;280:39337-45 pubmed
    ..These properties suggest that human topoisomerase IIalpha has the potential to alleviate torsional stress ahead of replication forks in an efficient and safe manner. ..
  44. Hadar T, Shvero J, Yaniv E, Shvili I, Leabu M, Koren R. Human topoisomerase II-alpha is highly expressed in sinonasal-inverted papilloma, but not in inflammatory polyp. J Cell Mol Med. 2008;12:1551-8 pubmed publisher
  45. Lamy P, Fina F, Bascoul Mollevi C, Laberenne A, Martin P, Ouafik L, et al. Quantification and clinical relevance of gene amplification at chromosome 17q12-q21 in human epidermal growth factor receptor 2-amplified breast cancers. Breast Cancer Res. 2011;13:R15 pubmed publisher
    ..reaction method and DNA extracted from frozen tumor specimens, 11 genes (MED1, STARD3, HER2, GRB7, THRA, RARA, TOP2A, IGFBP4, CCR7, KRT20, KRT19 and GAS), which are localized within Chr17q12-q21 and have a putative role in breast ..
  46. Durrieu F, Samejima K, Fortune J, Kandels Lewis S, Osheroff N, Earnshaw W. DNA topoisomerase IIalpha interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution. Curr Biol. 2000;10:923-6 pubmed
    ..In addition, we show that CAD binds to Topo IIalpha, and that their association enhances the decatenation activity of Topo IIalpha in vitro. ..
  47. Tsai S, Valkov N, Yang W, Gump J, Sullivan D, Seto E. Histone deacetylase interacts directly with DNA topoisomerase II. Nat Genet. 2000;26:349-53 pubmed
    ..Our results indicate the existence of a functionally coupled complex between these two enzymes and offer insights into the potential mechanisms of action of both enzymes. ..
  48. Guerin E, Entz Werle N, Eyer D, Pencreac h E, Schneider A, Falkenrodt A, et al. Modification of topoisomerase genes copy number in newly diagnosed childhood acute lymphoblastic leukemia. Leukemia. 2003;17:532-40 pubmed
    ..At diagnosis, allelic imbalance at topo-isomerase IIalpha (TOP2A) gene locus was found in 75% of informative cases whereas topoisomerase I and IIbeta gene loci are altered in none ..
  49. Leontiou C, Lightowlers R, Lakey J, Austin C. Kinetic analysis of human topoisomerase IIalpha and beta DNA binding by surface plasmon resonance. FEBS Lett. 2003;554:206-10 pubmed
    ..4 and 2.9 nM. We therefore conclude that neither isoform has any preference for a specific DNA substrate under the conditions used in these experiments. ..
  50. Lee C, Hague L, Li H, Donnelly R. Identification of toposome, a novel multisubunit complex containing topoisomerase IIalpha. Cell Cycle. 2004;3:638-47 pubmed
    ..These results suggest that toposome is a dynamic complex whose assembly or activation is subject to cell cycle regulation. ..
  51. Spence J, Phua H, Mills W, Carpenter A, Porter A, Farr C. Depletion of topoisomerase IIalpha leads to shortening of the metaphase interkinetochore distance and abnormal persistence of PICH-coated anaphase threads. J Cell Sci. 2007;120:3952-64 pubmed
  52. Nielsen K, Muller S, Møller S, Schønau A, Balslev E, Knoop A, et al. Aberrations of ERBB2 and TOP2A genes in breast cancer. Mol Oncol. 2010;4:161-8 pubmed publisher
    Copy number changes in TOP2A have frequently been linked to ERBB2 (HER2) amplified breast cancers...
  53. Nielsen K, Ejlertsen B, Møller S, Jensen M, Balslev E, Muller S, et al. Lack of independent prognostic and predictive value of centromere 17 copy number changes in breast cancer patients with known HER2 and TOP2A status. Mol Oncol. 2012;6:88-97 pubmed publisher
    The clinical benefit of anthracyclines has been connected to HER2 status, TOP2A status and centromere 17 copy numbers (CEN-17)...
  54. Hong Y, Sang M, Shang C, Xue Y, Liu Y. Quantitative analysis of topoisomerase II alpha and evaluation of its effects on cell proliferation and apoptosis in glioblastoma cancer stem cells. Neurosci Lett. 2012;518:138-43 pubmed publisher
    ..Topo-II? may be a novel marker of cell proliferation and/or survival factor in glioblastoma CSCs. It may be a potential target that will open up new opportunities to develop therapeutic strategies for gliomas. ..
  55. Sparano J, Goldstein L, Davidson N, Sledge G, Gray R. TOP2A RNA expression and recurrence in estrogen receptor-positive breast cancer. Breast Cancer Res Treat. 2012;134:751-7 pubmed publisher
    The purpose of this study is to evaluate the relationship between TOP2A RNA expression and recurrence in patients with operable estrogen receptor (ER)-positive breast cancer...
  56. Biersack H, Jensen S, Gromova I, Nielsen I, Westergaard O, Andersen A. Active heterodimers are formed from human DNA topoisomerase II alpha and II beta isoforms. Proc Natl Acad Sci U S A. 1996;93:8288-93 pubmed
    ..The natural existence of an active heterodimeric subclass of topoisomerase II merits attention whenever topoisomerases II alpha and II beta function, localization, and cell cycle regulation are investigated. ..
  57. Lang A, Mirski S, Cummings H, Yu Q, Gerlach J, Cole S. Structural organization of the human TOP2A and TOP2B genes. Gene. 1998;221:255-66 pubmed
    ..Human topoisomerase IIalpha (TOP2A) is encoded by the TOP2A gene on chromosome 17q21-22, and human topoisomerase IIbeta (TOP2B) is encoded by the ..
  58. Kurz E, Leader K, Kroll D, Clark M, Gieseler F. Modulation of human DNA topoisomerase IIalpha function by interaction with 14-3-3epsilon. J Biol Chem. 2000;275:13948-54 pubmed
    ..The association of topo II with 14-3-3 proteins does not extend to all 14-3-3 isoforms. No protein interaction or disruption of topo II function was observed with 14-3-3final sigma. ..
  59. Spence J, Critcher R, Ebersole T, Valdivia M, Earnshaw W, Fukagawa T, et al. Co-localization of centromere activity, proteins and topoisomerase II within a subdomain of the major human X alpha-satellite array. EMBO J. 2002;21:5269-80 pubmed
  60. Dawlaty M, Malureanu L, Jeganathan K, Kao E, Sustmann C, Tahk S, et al. Resolution of sister centromeres requires RanBP2-mediated SUMOylation of topoisomerase IIalpha. Cell. 2008;133:103-15 pubmed publisher
    ..Furthermore, mice with low amounts of RanBP2 are highly sensitive to tumor formation. Together, these data identify RanBP2 as a chromosomal instability gene that regulates Topo IIalpha by sumoylation and suppresses tumorigenesis. ..
  61. Coss A, Tosetto M, Fox E, Sapetto Rebow B, Gorman S, Kennedy B, et al. Increased topoisomerase IIalpha expression in colorectal cancer is associated with advanced disease and chemotherapeutic resistance via inhibition of apoptosis. Cancer Lett. 2009;276:228-38 pubmed publisher
    ..The influence of topoisomerase IIalpha gene (TOP2A) or protein alterations on disease progression and treatment response in colorectal cancer (CRC) is unknown...
  62. Yan S, Shun Chang J, Li C, Jie L, Ya Li L, Ling Xiong W. Topoisomerase II alpha expression and the benefit of adjuvant chemotherapy for postoperative patients with non-small cell lung cancer. BMC Cancer. 2010;10:621 pubmed publisher
    ..TopII? could be considered to be an independent prognostic biomarker of DFS in postoperative NSCLC patients who received adjuvant chemotherapy. ..
  63. Fountzilas G, Valavanis C, Kotoula V, Eleftheraki A, Kalogeras K, Tzaida O, et al. HER2 and TOP2A in high-risk early breast cancer patients treated with adjuvant epirubicin-based dose-dense sequential chemotherapy. J Transl Med. 2012;10:10 pubmed publisher
    HER2 and TOP2A parameters (gene status, mRNA and protein expression) have individually been associated with the outcome of patients treated with anthracyclines...
  64. Wells N, Fry A, Guano F, Norbury C, Hickson I. Cell cycle phase-specific phosphorylation of human topoisomerase II alpha. Evidence of a role for protein kinase C. J Biol Chem. 1995;270:28357-63 pubmed
    ..Our results implicate protein kinase C in the cell cycle phase-dependent modulation of topoisomerase II alpha enzymatic activity in human cells. ..
  65. Bronner C, Hopfner R, Mousli M. Transcriptional regulation of the human topoisomerase IIalpha gene. Anticancer Res. 2002;22:605-12 pubmed
    ..Here, we also speculate on the role of a novelprotein (named ICBP90) that has been identified by the one-hybrid system assay as a protein able to bind to these CCAAT sequences. ..
  66. Agostinho M, Rino J, Braga J, Ferreira F, Steffensen S, Ferreira J. Human topoisomerase IIalpha: targeting to subchromosomal sites of activity during interphase and mitosis. Mol Biol Cell. 2004;15:2388-400 pubmed
    ..Together, our data implicate several previously unsuspected activities in the partitioning of the enzyme between sites of activity and putative depots...
  67. Chekerov R, Klaman I, Zafrakas M, Könsgen D, Mustea A, Petschke B, et al. Altered expression pattern of topoisomerase IIalpha in ovarian tumor epithelial and stromal cells after platinum-based chemotherapy. Neoplasia. 2006;8:38-45 pubmed
    The aim of this study was to evaluate the expression of topoisomerase IIalpha (TOP2A) in epithelial and stromal cells of ovarian cancer...
  68. Nielsen K, Ejlertsen B, Møller S, Jørgensen J, Knoop A, Knudsen H, et al. The value of TOP2A gene copy number variation as a biomarker in breast cancer: Update of DBCG trial 89D. Acta Oncol. 2008;47:725-34 pubmed publisher
    Previous analyses of TOP2A and HER2 in the Danish Breast Cancer Coopererative Group (DBCG) trial 89D suggested that TOP2A amplifications and possible also deletions are predictive markers for the effect of adjuvant epirubicin in patients ..
  69. O Malley F, Chia S, Tu D, Shepherd L, Levine M, Bramwell V, et al. Topoisomerase II alpha and responsiveness of breast cancer to adjuvant chemotherapy. J Natl Cancer Inst. 2009;101:644-50 pubmed publisher
    Amplification or deletion of the topoisomerase II alpha (TOP2A) gene in breast cancers has been postulated to be more closely associated with responsiveness to anthracycline-containing chemotherapy than amplification of the human ..
  70. Wray J, Williamson E, Sheema S, Lee S, Libby E, Willman C, et al. Metnase mediates chromosome decatenation in acute leukemia cells. Blood. 2009;114:1852-8 pubmed publisher
    ..Thus, Metnase expression levels may predict AML resistance to Topo IIalpha inhibitors, and Metnase is a potential therapeutic target for small molecule interference. ..
  71. Konecny G, Pauletti G, Untch M, Wang H, Möbus V, Kuhn W, et al. Association between HER2, TOP2A, and response to anthracycline-based preoperative chemotherapy in high-risk primary breast cancer. Breast Cancer Res Treat. 2010;120:481-9 pubmed publisher
    ..response to anthracycline-based chemotherapy may be more likely related to the concomitant amplification of the TOP2A gene...
  72. Srikantan S, Abdelmohsen K, Lee E, Tominaga K, Subaran S, Kuwano Y, et al. Translational control of TOP2A influences doxorubicin efficacy. Mol Cell Biol. 2011;31:3790-801 pubmed publisher
    The cellular abundance of topoisomerase II? (TOP2A) critically maintains DNA topology after replication and determines the efficacy of TOP2 inhibitors in chemotherapy...
  73. Zaczek A, Markiewicz A, Supernat A, Bednarz Knoll N, Brandt B, Seroczynska B, et al. Prognostic value of TOP2A gene amplification and chromosome 17 polysomy in early breast cancer. Pathol Oncol Res. 2012;18:885-94 pubmed
    The aim of this study was to analyze the occurrence of TOP2A gene amplification and chromosome 17 polysomy in patients with early breast cancer and to correlate the status of these alterations with the prognostic significance expressed ..
  74. Chung T, Drake F, Tan K, Per S, Crooke S, Mirabelli C. Characterization and immunological identification of cDNA clones encoding two human DNA topoisomerase II isozymes. Proc Natl Acad Sci U S A. 1989;86:9431-5 pubmed
    ..These data provide genetic and immunochemical evidence for two Topo II isozymes. ..
  75. Meyer K, Kjeldsen E, Straub T, Knudsen B, Hickson I, Kikuchi A, et al. Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities. J Cell Biol. 1997;136:775-88 pubmed
    ..Scaffold-associated topoisomerase IIalpha appears not to be involved in catalytic DNA turnover, though it may play a role in the replicational cycle of centriols, where it accumulates during M phase. ..
  76. Endo H, Hirokawa M, Ishimaru N, Tanaka Y, Yamashita M, Sakaki M, et al. Unique cell membrane expression of topoisomerase-II alpha as a useful diagnostic marker of liposarcoma. Pathol Int. 2004;54:145-50 pubmed
    ..Immunostaining using the antibody for Topo-II alpha seems to be useful in recognizing lipoblasts that have been overlooked in hematoxylin-eosin-stained preparations, and is a useful marker for diagnosing liposarcoma. ..
  77. Varis A, Zaika A, Puolakkainen P, Nagy B, Madrigal I, Kokkola A, et al. Coamplified and overexpressed genes at ERBB2 locus in gastric cancer. Int J Cancer. 2004;109:548-53 pubmed
    ..for the amplicon formation because this region harbors the ERBB2 oncogene and several other targets, such as TOP2A and DARPP32...
  78. Dickey J, Osheroff N. Impact of the C-terminal domain of topoisomerase IIalpha on the DNA cleavage activity of the human enzyme. Biochemistry. 2005;44:11546-54 pubmed
    ..Therefore, the C-terminal domain of human topoisomerase IIalpha appears to play significant roles in modulating the DNA cleavage/ligation reaction of the enzyme and its response to anticancer agents. ..
  79. Li H, Wang Y, Liu X. Plk1-dependent phosphorylation regulates functions of DNA topoisomerase IIalpha in cell cycle progression. J Biol Chem. 2008;283:6209-21 pubmed publisher
  80. Glynn R, Mahon S, Curran C, Callagy G, Miller N, Kerin M. TOP2A amplification in the absence of that of HER-2/neu: toward individualization of chemotherapeutic practice in breast cancer. Oncologist. 2011;16:949-55 pubmed publisher
    ..relationship between human epidermal growth factor receptor (HER)-2/neu and the gene encoding topoisomerase II? (TOP2A) in breast cancer, while elucidating their association with clinicopathological variables...
  81. da Cunha I, De Brot L, Carvalho K, Rocha R, Fregnani J, Falzoni R, et al. Prognostication of soft tissue sarcomas based on chromosome 17q gene and protein status: evaluation of TOP2A, HER-2/neu, and survivin. Ann Surg Oncol. 2012;19:1790-9 pubmed publisher
    Topoisomerase 2 alpha (TOP2A), HER-2/neu, and survivin are genes that lie on chromosome 17 and correlate with the prognosis and prediction of target-driven therapy against tumors...
  82. Wang J, Xu B, Yuan P, Zhang P, Li Q, Ma F, et al. TOP2A amplification in breast cancer is a predictive marker of anthracycline-based neoadjuvant chemotherapy efficacy. Breast Cancer Res Treat. 2012;135:531-7 pubmed publisher
    Anthracycline is a DNA topoisomerase 2-? (TOP2A) inhibitor and its concomitant over expression with Human Epidermal Growth Factor Receptor 2 (HER2) was investigated of being predictive for the response to anthracycline-based ..
  83. Tan K, Dorman T, Falls K, Chung T, Mirabelli C, Crooke S, et al. Topoisomerase II alpha and topoisomerase II beta genes: characterization and mapping to human chromosomes 17 and 3, respectively. Cancer Res. 1992;52:231-4 pubmed
    ..We confirmed the chromosomal location of topo II alpha and mapped the topo II beta gene to chromosome 3. In addition, topo II beta exhibits genetic polymorphism as has been reported for topoisomerases I and II alpha. ..
  84. Bhat U, Raychaudhuri P, Beck W. Functional interaction between human topoisomerase IIalpha and retinoblastoma protein. Proc Natl Acad Sci U S A. 1999;96:7859-64 pubmed
    ..We conclude that topo IIalpha associates physically with Rb in interactions that appear to have functional significance. ..
  85. Shvero J, Koren R, Shvili I, Yaniv E, Sadov R, Hadar T. Expression of human DNA Topoisomerase II-alpha in squamous cell carcinoma of the larynx and its correlation with clinicopathologic variables. Am J Clin Pathol. 2008;130:934-9 pubmed publisher
    ..008) and tumor grade (P = .034) independently predicted disease-free survival. These findings suggest that high Topo II-alpha expression may be a useful indicator of tumor aggressiveness and poor outcome in laryngeal SCC. ..
  86. Kawamura R, Pope L, Christensen M, Sun M, Terekhova K, Boege F, et al. Mitotic chromosomes are constrained by topoisomerase II-sensitive DNA entanglements. J Cell Biol. 2010;188:653-63 pubmed publisher
    ..Our experiments show that DNA entanglements act in concert with protein-mediated compaction to fold chromatin into mitotic chromosomes. ..
  87. Gardner L, Malik R, Shimizu Y, Mullins N, ElShamy W. Geminin overexpression prevents the completion of topoisomerase II? chromosome decatenation, leading to aneuploidy in human mammary epithelial cells. Breast Cancer Res. 2011;13:R53 pubmed publisher
    ..On the basis of our findings, we propose that therapeutic targeting of geminin is essential for improving the therapeutic potential of TopoII? agents. ..
  88. Skouboe C, Bjergbaek L, Oestergaard V, Larsen M, Knudsen B, Andersen A. A human topoisomerase II alpha heterodimer with only one ATP binding site can go through successive catalytic cycles. J Biol Chem. 2003;278:5768-74 pubmed
    ..The results can be explained in a model, where efficient catalysis requires an extensive communication between the second ATP and the DNA segment to be cleaved. ..
  89. Arriola E, Marchio C, Tan D, Drury S, Lambros M, Natrajan R, et al. Genomic analysis of the HER2/TOP2A amplicon in breast cancer and breast cancer cell lines. Lab Invest. 2008;88:491-503 pubmed publisher
    HER2 and TOP2A are targets for the therapeutic agents trastuzumab and anthracyclines and are frequently amplified in breast cancers...
  90. Toyoda E, Kagaya S, Cowell I, Kurosawa A, Kamoshita K, Nishikawa K, et al. NK314, a topoisomerase II inhibitor that specifically targets the alpha isoform. J Biol Chem. 2008;283:23711-20 pubmed publisher
    Topoisomerase II (Top2) is a ubiquitous nuclear enzyme that relieves torsional stress in chromosomal DNA during various cellular processes...
  91. Stros M, Polanská E, Struncová S, Pospisilova S. HMGB1 and HMGB2 proteins up-regulate cellular expression of human topoisomerase IIalpha. Nucleic Acids Res. 2009;37:2070-86 pubmed publisher
  92. Zaczek A, Markiewicz A, Seroczynska B, Skokowski J, Jaskiewicz J, Pienkowski T, et al. Prognostic significance of TOP2A gene dosage in HER-2-negative breast cancer. Oncologist. 2012;17:1246-55 pubmed publisher
    ..growth factor receptor 2 (HER-2) gene alterations analyzed separately and jointly with topoisomerase II ? (TOP2A) gene alterations; however, the role of TOP2A gene abnormalities alone has not been thoroughly investigated...