retinoblastoma genes


Summary: Tumor suppressor genes located on human chromosome 13 in the region 13q14 and coding for a family of phosphoproteins with molecular weights ranging from 104 kDa to 115 kDa. One copy of the wild-type Rb gene is necessary for normal retinal development. Loss or inactivation of both alleles at this locus results in retinoblastoma.

Top Publications

  1. Robinson G, Wagner K, Hennighausen L. Functional mammary gland development and oncogene-induced tumor formation are not affected by the absence of the retinoblastoma gene. Oncogene. 2001;20:7115-9 pubmed
  2. Jiang Z, Zacksenhaus E, Gallie B, Phillips R. The retinoblastoma gene family is differentially expressed during embryogenesis. Oncogene. 1997;14:1789-97 pubmed
    ..Our results suggest that members of RB1 gene family have distinct, but overlapping roles in embryogenesis, with p107 and RB1 possibly having redundant functions in the central nervous system and liver. ..
  3. Lara M, Santos M, Ruiz S, Segrelles C, Moral M, Martínez Cruz A, et al. p107 acts as a tumor suppressor in pRb-deficient epidermis. Mol Carcinog. 2008;47:105-13 pubmed
    ..Overall, our data demonstrate that p107 behaves as a tumor suppressor in epidermis in the absence of pRb and suggest novel tumor-suppressive roles for p107 in the context of functional p53 and activated Ras. ..
  4. Chen G, Guy C, Chen H, Hu N, Lee E, Lee W. Molecular cloning and developmental expression of mouse p130, a member of the retinoblastoma gene family. J Biol Chem. 1996;271:9567-72 pubmed
    ..Our data are consistent with the hypothesis that p130 and p107 do not compensate for the loss of Rb and support the view that p130 is related to, yet distinct from, the RB gene. ..
  5. Paggi M, Giordano A. Who is the boss in the retinoblastoma family? The point of view of Rb2/p130, the little brother. Cancer Res. 2001;61:4651-4 pubmed
    ..Finally, we take into consideration the data provided by the targeted disruption of each RB family gene, alone or in combination, in the mouse model. ..
  6. Thomas D, Carty S, Piscopo D, Lee J, Wang W, Forrester W, et al. The retinoblastoma protein acts as a transcriptional coactivator required for osteogenic differentiation. Mol Cell. 2001;8:303-16 pubmed
    ..Thus, pRb functions as a direct transcriptional coactivator promoting osteoblast differentiation, which may contribute to the targeting of pRb in osteosarcoma. ..
  7. Ferguson K, Vanderluit J, Hebert J, McIntosh W, Tibbo E, Maclaurin J, et al. Telencephalon-specific Rb knockouts reveal enhanced neurogenesis, survival and abnormal cortical development. EMBO J. 2002;21:3337-46 pubmed
  8. Ramprasad V, Madhavan J, Murugan S, Sujatha J, Suresh S, Sharma T, et al. Retinoblastoma in India : microsatellite analysis and its application in genetic counseling. Mol Diagn Ther. 2007;11:63-70 pubmed
    ..In tertiary ophthalmic practice in India, there is an emerging trend towards the application of genetical knowledge in clinical practice. ..
  9. Harrington E, Bruce J, Harlow E, Dyson N. pRB plays an essential role in cell cycle arrest induced by DNA damage. Proc Natl Acad Sci U S A. 1998;95:11945-50 pubmed
    ..Furthermore, because many cancer therapies act by damaging DNA, these findings also have implications for the treatment of tumors in which pRB is inactivated. ..

More Information


  1. Sage J, Miller A, Perez Mancera P, Wysocki J, Jacks T. Acute mutation of retinoblastoma gene function is sufficient for cell cycle re-entry. Nature. 2003;424:223-8 pubmed
    ..Thus, the use of conditional knockout strategies might refine our understanding of gene function and help to model human cancer more accurately. ..
  2. Ahuja D, Sáenz Robles M, Pipas J. SV40 large T antigen targets multiple cellular pathways to elicit cellular transformation. Oncogene. 2005;24:7729-45 pubmed
  3. Condorelli G, Giordano A. Synergistic role of E1A-binding proteins and tissue-specific transcription factors in differentiation. J Cell Biochem. 1997;67:423-31 pubmed
    ..We provide here an update on the recent advances in this field and some models of interaction between E1A binding protein and tissue-specific transcription factors. ..
  4. Richter S, Vandezande K, Chen N, Zhang K, Sutherland J, Anderson J, et al. Sensitive and efficient detection of RB1 gene mutations enhances care for families with retinoblastoma. Am J Hum Genet. 2003;72:253-69 pubmed
    ..Moreover, health care savings continue to accrue, as children in succeeding generations avoid unnecessary repeated anaesthetics and examinations. ..
  5. Black E, Huang E, Dressman H, Rempel R, Laakso N, Asa S, et al. Distinct gene expression phenotypes of cells lacking Rb and Rb family members. Cancer Res. 2003;63:3716-23 pubmed
    ..We suggest that this is an approach to the eventual understanding of gene regulatory pathways that define a phenotypic state, including those events that lead to tumor development. ..
  6. Morris E, Dyson N. Retinoblastoma protein partners. Adv Cancer Res. 2001;82:1-54 pubmed
    ..How many functions does pRb possess, which of these functions are important for development, and which contribute to tumor suppression? The goal of this review is to summarize the current literature of pRb-associated proteins. ..
  7. Baldi A, Boccia V, Claudio P, De Luca A, Giordano A. Genomic structure of the human retinoblastoma-related Rb2/p130 gene. Proc Natl Acad Sci U S A. 1996;93:4629-32 pubmed
    ..This study provides the molecular basis for understanding the transcriptional control of the Rb2/p130 gene and for implementing a comprehensive Rb2/p130 mutation screen using genomic DNA as a template. ..
  8. Zacksenhaus E, Jiang Z, Chung D, Marth J, Phillips R, Gallie B. pRb controls proliferation, differentiation, and death of skeletal muscle cells and other lineages during embryogenesis. Genes Dev. 1996;10:3051-64 pubmed
    ..These results demonstrate a role for pRb during terminal differentiation of skeletal muscles in vivo and place pRb at a nodal point that controls cell proliferation, differentiation, and death. ..
  9. Pertile P, Baldi A, De Luca A, Bagella L, Virgilio L, Pisano M, et al. Molecular cloning, expression, and developmental characterization of the murine retinoblastoma-related gene Rb2/p130. Cell Growth Differ. 1995;6:1659-64 pubmed
    ..In developing mouse embryos, the Rb2/p130 protein is expressed as early as day 10 of gestation and reached a peak of expression around day 13 of gestation, implying a developmental regulation of the Rb2/p130 gene in murine ontogeny. ..
  10. Herschkowitz J, He X, Fan C, Perou C. The functional loss of the retinoblastoma tumour suppressor is a common event in basal-like and luminal B breast carcinomas. Breast Cancer Res. 2008;10:R75 pubmed publisher
    ..These results suggest that the functional loss of RB1 is common in basal-like tumours, which may play a key role in dictating their aggressive biology and unique therapeutic responses. ..
  11. Marino S, Vooijs M, van der Gulden H, Jonkers J, Berns A. Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum. Genes Dev. 2000;14:994-1004 pubmed
    ..Our results demonstrate that loss of function of RB is essential for medulloblastoma development in the mouse and strongly support the hypothesis that medulloblastomas arise from multipotent precursor cells located in the EGL. ..
  12. Ziebold U, Reza T, Caron A, Lees J. E2F3 contributes both to the inappropriate proliferation and to the apoptosis arising in Rb mutant embryos. Genes Dev. 2001;15:386-91 pubmed
    ..Thus, contrary to the prevailing view of E2F action, E2F3 makes a major contribution to the apoptosis resulting from pRB loss. ..
  13. Semczuk A, Marzec B, Roessner A, Jakowicki J, Wojcierowski J, Schneider Stock R. Loss of heterozygosity of the retinoblastoma gene is correlated with the altered pRb expression in human endometrial cancer. Virchows Arch. 2002;441:577-83 pubmed
    ..Our data suggest that LOH at the Rb locus plays a role in the oncogenesis of a subset of uterine neoplasms and corresponds with the altered expression of the pRb. ..
  14. Flesken Nikitin A, Choi K, Eng J, Shmidt E, Nikitin A. Induction of carcinogenesis by concurrent inactivation of p53 and Rb1 in the mouse ovarian surface epithelium. Cancer Res. 2003;63:3459-63 pubmed
    ..These results establish critical interactions between p53 and Rb1 pathways in EOC pathogenesis, and provide a genetically defined immunocompetent mouse model of sporadic EOC. ..
  15. Wu X. Urothelial tumorigenesis: a tale of divergent pathways. Nat Rev Cancer. 2005;5:713-25 pubmed
    ..Correcting pathway-specific defects represents an attractive strategy for the molecular therapy of urothelial carcinomas. ..
  16. Tsai K, Hu Y, Macleod K, Crowley D, Yamasaki L, Jacks T. Mutation of E2f-1 suppresses apoptosis and inappropriate S phase entry and extends survival of Rb-deficient mouse embryos. Mol Cell. 1998;2:293-304 pubmed
    ..0 with anemia and defective skeletal muscle and lung development, demonstrating that E2F-1 regulation is not the sole function of pRB in development. ..
  17. Dyer M, Bremner R. The search for the retinoblastoma cell of origin. Nat Rev Cancer. 2005;5:91-101 pubmed
    ..Identifying the cell of origin for this tumour would advance our understanding of how cellular context affects the requirement of specific mutations for cancer initiation and progression. ..
  18. MacPherson D, Sage J, Kim T, Ho D, McLaughlin M, Jacks T. Cell type-specific effects of Rb deletion in the murine retina. Genes Dev. 2004;18:1681-94 pubmed
    ..Conditional Rb mutation in the retina did not result in retinoblastoma formation even in a p53-mutant background. However, on a p107- or p130-deficient background, Rb mutation in the retina caused retinal dysplasia or retinoblastoma. ..
  19. Lee M, Williams B, Mulligan G, Mukai S, Bronson R, Dyson N, et al. Targeted disruption of p107: functional overlap between p107 and Rb. Genes Dev. 1996;10:1621-32 pubmed
    ..These results provide the first in vivo evidence that p107 and Rb have overlapping functions in some tissues of the developing and adult mouse...
  20. MacPherson D, Sage J, Crowley D, Trumpp A, Bronson R, Jacks T. Conditional mutation of Rb causes cell cycle defects without apoptosis in the central nervous system. Mol Cell Biol. 2003;23:1044-53 pubmed
    ..These data support a model in which hypoxia is a necessary cofactor in the death of CNS neurons in the developing Rb mutant embryo. ..
  21. Zhou Z, Flesken Nikitin A, Corney D, Wang W, Goodrich D, Roy Burman P, et al. Synergy of p53 and Rb deficiency in a conditional mouse model for metastatic prostate cancer. Cancer Res. 2006;66:7889-98 pubmed
    ..The new genetically defined model should be particularly valuable for providing new molecular insights into the pathogenesis of human prostate cancer. ..
  22. Choy K, Pang C, Yu C, Wong H, Ng J, Fan D, et al. Loss of heterozygosity and mutations are the major mechanisms of RB1 gene inactivation in Chinese with sporadic retinoblastoma. Hum Mutat. 2002;20:408 pubmed
    ..Our results indicate that the RB1 gene in sporadic retinoblastoma is commonly inactivated because of loss-of-function mutations and loss of heterozygosity but not by the epigenetic phenomenon of promoter hypermethylation. ..
  23. Jacks T, Fazeli A, Schmitt E, Bronson R, Goodell M, Weinberg R. Effects of an Rb mutation in the mouse. Nature. 1992;359:295-300 pubmed
    ..Embryos homozygous for the mutation die between days 14 and 15 of gestation, exhibiting neuronal cell death and defective erythropoiesis. ..
  24. Clarke A, Maandag E, van Roon M, van der Lugt N, van der Valk M, Hooper M, et al. Requirement for a functional Rb-1 gene in murine development. Nature. 1992;359:328-30 pubmed
    ..However, homozygous mutant embryos fail to reach term and show a number of abnormalities in neural and haematopoietic development. Broadly similar results are reported by the other groups. ..
  25. Williams B, Remington L, Albert D, Mukai S, Bronson R, Jacks T. Cooperative tumorigenic effects of germline mutations in Rb and p53. Nat Genet. 1994;7:480-4 pubmed
    ..These data indicate that mutations in Rb and p53 can cooperate in the transformation of certain cell types in the mouse...
  26. te Riele H, Maandag E, Berns A. Highly efficient gene targeting in embryonic stem cells through homologous recombination with isogenic DNA constructs. Proc Natl Acad Sci U S A. 1992;89:5128-32 pubmed
    ..This result indicates that, also in mammalian cells, homologous recombination rather than random integration can be the predominant event. ..
  27. Miyamoto H, Shuin T, Torigoe S, Iwasaki Y, Kubota Y. Retinoblastoma gene mutations in primary human bladder cancer. Br J Cancer. 1995;71:831-5 pubmed
    ..These results suggest that RB gene mutations are involved in low-grade and superficial bladder cancers as well as in high-grade and invasive cancers. ..
  28. Blanquet V, Turleau C, Gross Morand M, Senamaud Beaufort C, Doz F, Besmond C. Spectrum of germline mutations in the RB1 gene: a study of 232 patients with hereditary and non hereditary retinoblastoma. Hum Mol Genet. 1995;4:383-8 pubmed
    ..The spectrum of mutations presented here should help to improve the clinical management of retinoblastoma and to understand the molecular mechanisms leading to tumorigenesis. ..
  29. Okamoto A, Demetrick D, Spillare E, Hagiwara K, Hussain S, Bennett W, et al. Mutations and altered expression of p16INK4 in human cancer. Proc Natl Acad Sci U S A. 1994;91:11045-9 pubmed
  30. Lee E, Hu N, Yuan S, Cox L, Bradley A, Lee W, et al. Dual roles of the retinoblastoma protein in cell cycle regulation and neuron differentiation. Genes Dev. 1994;8:2008-21 pubmed
    ..Taken together, these results suggest that the p110RB protein not only regulates progression through the cell cycle but is also important for cell survival and differentiation. ..
  31. Hiebert S, Chellappan S, Horowitz J, Nevins J. The interaction of RB with E2F coincides with an inhibition of the transcriptional activity of E2F. Genes Dev. 1992;6:177-85 pubmed
    ..A mutant pRB protein that does not associate with E2F does not inhibit transcription. We conclude that as a consequence of its interaction with E2F, pRB may regulate the transcriptional function of the E2F factor. ..
  32. Almasan A, Yin Y, Kelly R, Lee E, Bradley A, Li W, et al. Deficiency of retinoblastoma protein leads to inappropriate S-phase entry, activation of E2F-responsive genes, and apoptosis. Proc Natl Acad Sci U S A. 1995;92:5436-40 pubmed
  33. Mayol X, Grana X, Baldi A, Sang N, Hu Q, Giordano A. Cloning of a new member of the retinoblastoma gene family (pRb2) which binds to the E1A transforming domain. Oncogene. 1993;8:2561-6 pubmed
    ..Interestingly, pRb2 fails to bind an E1A mutant in the transforming domain 2 suggesting that pRb2 is involved in the transforming capacity of E1A. ..
  34. Lee E, Chang C, Hu N, Wang Y, Lai C, Herrup K, et al. Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis. Nature. 1992;359:288-94 pubmed
    ..All spinal ganglion cells die, but the neural retina is unaffected. Transfer of the human retinoblastoma (RB) mini-transgene into the mutant mice corrects the developmental defects. Thus, Rb is essential for normal mouse development. ..
  35. Williams B, Schmitt E, Remington L, Bronson R, Albert D, Weinberg R, et al. Extensive contribution of Rb-deficient cells to adult chimeric mice with limited histopathological consequences. EMBO J. 1994;13:4251-9 pubmed
    ..Like animals heterozygous for the Rb mutation, the chimeras develop tumors of the intermediate lobe of the pituitary, and the rate of pituitary tumorigenesis is greatly accelerated. ..
  36. Maandag E, van der Valk M, Vlaar M, Feltkamp C, O Brien J, van Roon M, et al. Developmental rescue of an embryonic-lethal mutation in the retinoblastoma gene in chimeric mice. EMBO J. 1994;13:4260-8 pubmed
    ..Moreover, the formation of lens fibre cells was severely disturbed. No retinoblastomas developed in any of these mice. Instead, nearly all animals died of pituitary gland tumours which were exclusively derived from Rb-1- cells. ..
  37. Knudsen E, Knudsen K. Retinoblastoma tumor suppressor: where cancer meets the cell cycle. Exp Biol Med (Maywood). 2006;231:1271-81 pubmed
    ..This review details facets of RB protein function in cell cycle control and focuses on specific questions that remain intensive areas of investigation. ..
  38. Muthusamy V, Hobbs C, Nogueira C, Cordon Cardo C, McKee P, Chin L, et al. Amplification of CDK4 and MDM2 in malignant melanoma. Genes Chromosomes Cancer. 2006;45:447-54 pubmed
    ..These results suggest that coamplification of CDK4 and MDM2 may substitute for loss of P16INK4A and P14ARF function in a subset of melanomas. ..
  39. Eason D, Coppola D, Livingston S, Shepherd A, Blanck G. Loss of MHC class II inducibility in hyperplastic tissue in Rb-defective mice. Cancer Lett. 2001;171:209-14 pubmed
    ..MHC class II IAbeta is not induced by IFN-gamma in Rb-deficient neoplastic cells, but remains inducible in related normal tissue. ..
  40. Nikitin A, Riley D, Lee W. A paradigm for cancer treatment using the retinoblastoma gene in a mouse model. Ann N Y Acad Sci. 1999;886:12-22 pubmed
    ..These results fulfill a promise of cancer treatment by reconstitution of tumor suppressor function. ..
  41. Sabelli P, Hoerster G, Lizarraga L, Brown S, Gordon Kamm W, Larkins B. Positive regulation of minichromosome maintenance gene expression, DNA replication, and cell transformation by a plant retinoblastoma gene. Proc Natl Acad Sci U S A. 2009;106:4042-7 pubmed publisher
    ..Our results indicate a cell cycle pathway in maize, in which 2 RBR genes have specific and opposing functions. Thus, the paradigm that RBR genes are negative cell cycle regulators cannot be considered universal...
  42. Scheffer H, Imhof S, Moll A. [From gene to disease; retinoblastoma and the RB1 gene]. Ned Tijdschr Geneeskd. 2001;145:1245-7 pubmed
    ..Molecular diagnosis is performed by a complete scanning of the RB1 coding sequence which includes flanking intronic sequences. Approximately 85% of pathogenic mutations can be identified. ..
  43. Karsten S, Kudo L, Jackson R, Sabatti C, Kornblum H, Geschwind D. Global analysis of gene expression in neural progenitors reveals specific cell-cycle, signaling, and metabolic networks. Dev Biol. 2003;261:165-82 pubmed
    ..We propose a putative network of gene expression linking cell cycle control to cell fate pathways, providing a framework for further investigations of neural stem cell proliferation and differentiation. ..
  44. Skotheim R, Lothe R. The testicular germ cell tumour genome. APMIS. 2003;111:136-50; discussion 50-1 pubmed
  45. Lan J, Xiong Y, Lin Y, Wang B, Gong L, Xu H, et al. Helicobacter pylori infection generated gastric cancer through p53-Rb tumor-suppressor system mutation and telomerase reactivation. World J Gastroenterol. 2003;9:54-8 pubmed
  46. Romagnoli S, Roncalli M, Graziani D, Cassani B, Roz E, Bonavina L, et al. Molecular alterations of Barrett's esophagus on microdissected endoscopic biopsies. Lab Invest. 2001;81:241-7 pubmed
    ..Some of them precede the development of intestinal metaplasia, suggesting that genetic alterations take place earlier than previously thought. ..
  47. Diaz Cano S, Blanes A, Rubio J, Matilla A, Wolfe H. Molecular evolution and intratumor heterogeneity by topographic compartments in muscle-invasive transitional cell carcinoma of the urinary bladder. Lab Invest. 2000;80:279-89 pubmed
    ..No differences in the immunohistochemical expression were observed, precluding a more extensive clinical application. ..
  48. Mitra A, Datar R, Cote R. Molecular staging of bladder cancer. BJU Int. 2005;96:7-12 pubmed
  49. Mittendorf E, McHenry C. Parathyroid carcinoma. J Surg Oncol. 2005;89:136-42 pubmed
  50. Matsumoto H, Kobayashi O, Tamura K, Sekine I, Yamamoto M. Novel germline mutation in the RB1 gene with multifocal bone tumors following retinoblastoma. Pediatr Int. 2003;45:728-30 pubmed
  51. Nikitin A, Liu C, Flesken Nikitin A, Chen C, Chen P, Lee W. Cell lineage-specific effects associated with multiple deficiencies of tumor susceptibility genes in Msh2(-/-)Rb(+/-) mice. Cancer Res. 2002;62:5134-8 pubmed
    ..Taken together, these data not only revealed a novel biological interaction between Rb and Msh2 but also cell lineage specificity effects associated with multiple deficiencies in these tumor susceptibility genes. ..
  52. Lohmann D, Gerick M, Brandt B, Oelschläger U, Lorenz B, Passarge E, et al. Constitutional RB1-gene mutations in patients with isolated unilateral retinoblastoma. Am J Hum Genet. 1997;61:282-94 pubmed
    ..In conclusion, our results emphasize that the manifestation and transmissibility of retinoblastoma depend on the nature of the first mutation, its time in development, and the number and types of cells that are affected. ..
  53. Pradhan M, Ng Y, Strickland A, George P, Raizis A, Warrington J, et al. Role of genetic testing in retinoblastoma management at a tertiary referral centre. Clin Exp Ophthalmol. 2010;38:231-6 pubmed publisher
    ..Retinoblastoma (MIM +180 200) is a malignant neoplasm affecting embryonal retina, associated with mutations in the RB1 gene. This paper investigates the results of RB1 testing in retinoblastoma management in a tertiary referral centre...