Fhit

Summary

Gene Symbol: Fhit
Description: fragile histidine triad gene
Alias: AW045638, Fra14A2, bis(5'-adenosyl)-triphosphatase, AP3A hydrolase, AP3Aase, diadenosine 5',5'''-P1,P3-triphosphate hydrolase, dinucleosidetriphosphatase, fragile histidine triad protein
Species: mouse
Products:     Fhit

Top Publications

  1. Fong L, Fidanza V, Zanesi N, Lock L, Siracusa L, Mancini R, et al. Muir-Torre-like syndrome in Fhit-deficient mice. Proc Natl Acad Sci U S A. 2000;97:4742-7 pubmed
    To investigate the role of the Fhit gene in carcinogen induction of neoplasia, we have inactivated one Fhit allele in mouse embryonic stem cells and produced (129/SvJ x C57BL/6J) F(1) mice with a Fhit allele inactivated (+/-)...
  2. Zanesi N, Fidanza V, Fong L, Mancini R, Druck T, Valtieri M, et al. The tumor spectrum in FHIT-deficient mice. Proc Natl Acad Sci U S A. 2001;98:10250-5 pubmed
    Mice carrying one inactivated Fhit allele (Fhit +/- mice) are highly susceptible to tumor induction by N-nitrosomethylbenzylamine, with 100% of Fhit +/- mice exhibiting tumors of the forestomach/squamocolumnar junction vs...
  3. Barnes L, Garrison P, Siprashvili Z, Guranowski A, Robinson A, Ingram S, et al. Fhit, a putative tumor suppressor in humans, is a dinucleoside 5',5"'-P1,P3-triphosphate hydrolase. Biochemistry. 1996;35:11529-35 pubmed
    ..histidines are required for full activity, and the central histidine of the triad is absolutely essential for Ap3A hydrolase activity...
  4. Saldivar J, Miuma S, Bene J, Hosseini S, Shibata H, Sun J, et al. Initiation of genome instability and preneoplastic processes through loss of Fhit expression. PLoS Genet. 2012;8:e1003077 pubmed publisher
    ..A frequent, perhaps earliest, genetic alteration in preneoplasias is deletion within the fragile FRA3B/FHIT locus, leading to loss of Fhit protein expression...
  5. Matsuyama A, Shiraishi T, Trapasso F, Kuroki T, Alder H, Mori M, et al. Fragile site orthologs FHIT/FRA3B and Fhit/Fra14A2: evolutionarily conserved but highly recombinogenic. Proc Natl Acad Sci U S A. 2003;100:14988-93 pubmed
    ..The FHIT gene, encompassing the FRA3B region, is a tumor-suppressor gene...
  6. Ohta M, Inoue H, Cotticelli M, Kastury K, Baffa R, Palazzo J, et al. The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers. Cell. 1996;84:587-97 pubmed
    ..Exon amplification from cosmids covering this deleted region allowed identification of the human FHIT gene, a member of ther histidine triad gene family, which encodes a protein with 69% similarity to an S...
  7. Dumon K, Ishii H, Fong L, Zanesi N, Fidanza V, Mancini R, et al. FHIT gene therapy prevents tumor development in Fhit-deficient mice. Proc Natl Acad Sci U S A. 2001;98:3346-51 pubmed
    The tumor suppressor gene FHIT spans a common fragile site and is highly susceptible to environmental carcinogens. FHIT inactivation and loss of expression is found in a large fraction of premaligant and malignant lesions...
  8. Ishii H, Mimori K, Ishikawa K, Okumura H, Pichiorri F, Druck T, et al. Fhit-deficient hematopoietic stem cells survive hydroquinone exposure carrying precancerous changes. Cancer Res. 2008;68:3662-70 pubmed publisher
    The fragile FHIT gene is among the first targets of DNA damage in preneoplastic lesions, and recent studies have shown that Fhit protein is involved in surveillance of genome integrity and checkpoint response after genotoxin exposure...
  9. Zanesi N, Mancini R, Sevignani C, Vecchione A, Kaou M, Valtieri M, et al. Lung cancer susceptibility in Fhit-deficient mice is increased by Vhl haploinsufficiency. Cancer Res. 2005;65:6576-82 pubmed
    The FHIT gene plays important roles in cancer development, including lung cancers, in which the Fhit protein is frequently lost...

More Information

Publications38

  1. Sun J, Okumura H, Yearsley M, Frankel W, Fong L, Druck T, et al. Nit1 and Fhit tumor suppressor activities are additive. J Cell Biochem. 2009;107:1097-106 pubmed publisher
    The fragile histidine triad gene (human FHIT, mouse Fhit) has been shown to act as a tumor suppressor gene...
  2. De Flora S, D Agostini F, Izzotti A, Zanesi N, Croce C, Balansky R. Molecular and cytogenetical alterations induced by environmental cigarette smoke in mice heterozygous for Fhit. Cancer Res. 2007;67:1001-6 pubmed
    Previous studies in humans and animal models provided evidence that the Fhit gene is an early target for cigarette smoke...
  3. Karras J, Schrock M, Batar B, Zhang J, La Perle K, Druck T, et al. Fhit loss-associated initiation and progression of neoplasia in vitro. Cancer Sci. 2016;107:1590-1598 pubmed publisher
    The FHIT gene, encompassing an active common fragile site, FRA3B, is frequently silenced in preneoplasia and cancer, through gene rearrangement or methylation of regulatory sequences...
  4. Paisie C, Schrock M, Karras J, Zhang J, Miuma S, Ouda I, et al. Exome-wide single-base substitutions in tissues and derived cell lines of the constitutive Fhit knockout mouse. Cancer Sci. 2016;107:528-35 pubmed publisher
    Loss of expression of Fhit, a tumor suppressor and genome caretaker, occurs in preneoplastic lesions during development of many human cancers...
  5. Saldivar J, Bene J, Hosseini S, Miuma S, Horton S, Heerema N, et al. Characterization of the role of Fhit in suppression of DNA damage. Adv Biol Regul. 2013;53:77-85 pubmed publisher
    The fragile histidine triad protein, Fhit, has a number of reported tumor suppressive functions which include signaling of apoptosis in cancer cells in vitro and in vivo, modulation of the DNA damage response, down-regulation of target ..
  6. Zanesi N, Pekarsky Y, Croce C. A mouse model of the fragile gene FHIT: From carcinogenesis to gene therapy and cancer prevention. Mutat Res. 2005;591:103-9 pubmed
    ..The mouse Fhit ortholog is also located at a common fragile site, Fra14A2 on murine chromosome 14, and sustains homozygous deletions in murine cancer cell lines...
  7. Vecchione A, Sevignani C, Giarnieri E, Zanesi N, Ishii H, Cesari R, et al. Inactivation of the FHIT gene favors bladder cancer development. Clin Cancer Res. 2004;10:7607-12 pubmed
    The fragile histidine triad (FHIT) gene located on chromosome 3p14.2 is frequently deleted in human tumors...
  8. Ishii H, Mimori K, Inageta T, Murakumo Y, Vecchione A, Mori M, et al. Components of DNA damage checkpoint pathway regulate UV exposure-dependent alterations of gene expression of FHIT and WWOX at chromosome fragile sites. Mol Cancer Res. 2005;3:130-8 pubmed
    ..that not only genetic but also epigenetic alterations in cancerous cells are involved in inactivation of the genes FHIT and WWOX at chromosome fragile sites, reported to be potential tumor suppressor genes...
  9. Shiraishi T, Druck T, Mimori K, Flomenberg J, Berk L, Alder H, et al. Sequence conservation at human and mouse orthologous common fragile regions, FRA3B/FHIT and Fra14A2/Fhit. Proc Natl Acad Sci U S A. 2001;98:5722-7 pubmed
    ..This study describes a comparison of orthologous fragile regions, the human FRA3B/FHIT and the murine Fra14A2/Fhit locus...
  10. Date H, Onodera O, Tanaka H, Iwabuchi K, Uekawa K, Igarashi S, et al. Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. Nat Genet. 2001;29:184-8 pubmed
    ..We have called its product aprataxin; the gene symbol is APTX. Although many HIT proteins have been identified, aprataxin is the first to be linked to a distinct phenotype...
  11. Pekarsky Y, Campiglio M, Siprashvili Z, Druck T, Sedkov Y, Tillib S, et al. Nitrilase and Fhit homologs are encoded as fusion proteins in Drosophila melanogaster and Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1998;95:8744-9 pubmed
    The tumor suppressor gene FHIT encompasses the common human chromosomal fragile site at 3p14.2 and numerous cancer cell biallelic deletions...
  12. Sun J, Liu J, Pan X, Quimby D, Zanesi N, Druck T, et al. Effect of zinc supplementation on N-nitrosomethylbenzylamine-induced forestomach tumor development and progression in tumor suppressor-deficient mouse strains. Carcinogenesis. 2011;32:351-8 pubmed publisher
    ..0 versus 5.0 tumors for Zn supplemented (P < 0.05); Zn-supplemented Fhit-/- mice averaged 5.7 versus 8.0 for control mice (P < 0.01); Zn-supplemented Fhit-/-Nit1-/- mice averaged 5...
  13. McCorkell K, Mancini R, Siprashvili Z, Barnoski B, Iliopoulos D, Siracusa L, et al. Influence of a nonfragile FHIT transgene on murine tumor susceptibility. Cytogenet Genome Res. 2007;118:196-203 pubmed
    b>FHIT, at a constitutively active chromosome fragile site, is often a target of chromosomal aberrations and deletion in a large fraction of human tumors...
  14. Ishii H, Mimori K, Inoue H, Inageta T, Ishikawa K, Semba S, et al. Fhit modulates the DNA damage checkpoint response. Cancer Res. 2006;66:11287-92 pubmed
    In preneoplastic lesions, the DNA damage checkpoint is induced and loss of heterozygosity at the FRA3B/FHIT common chromosome fragile region precedes or is coincident with activation of the checkpoint response in these early stages...
  15. Hu B, Wang H, Wang X, Lu H, Huang C, Powell S, et al. Fhit and CHK1 have opposing effects on homologous recombination repair. Cancer Res. 2005;65:8613-6 pubmed
    Fragile histidine triad (FHIT) gene deletion or promoter methylation and reduced Fhit protein expression occur in approximately 70% of human epithelial tumors and, in some cancers, are clearly associated with tumor progression...
  16. Korsisaari N, Rossi D, Luukko K, Huebner K, Henkemeyer M, Makela T. The histidine triad protein Hint is not required for murine development or Cdk7 function. Mol Cell Biol. 2003;23:3929-35 pubmed
    ..within the HIT family was addressed by crossing Hint(-/-) mice with mice lacking the related HIT protein, Fhit, and by assaying the expression levels of the HIT protein gene family members Hint2 and Hint3 in Hint(+/+) and Hint(..
  17. Hu B, Ying X, Wang J, Piriyapongsa J, Jordan I, Sheng J, et al. Identification of a tumor-suppressive human-specific microRNA within the FHIT tumor-suppressor gene. Cancer Res. 2014;74:2283-94 pubmed publisher
    Loss or attenuated expression of the tumor-suppressor gene FHIT is associated paradoxically with poor progression of human tumors...
  18. Pekarsky Y, Druck T, Cotticelli M, Ohta M, Shou J, Mendrola J, et al. The murine Fhit locus: isolation, characterization, and expression in normal and tumor cells. Cancer Res. 1998;58:3401-8 pubmed
    The murine Fhit locus maps near the centromere nu proximal Ptprg locus on mouse chromosome 14. The cDNA sequence and structure are similar to those of the human gene, with exons 5-9 encoding the protein...
  19. Arlt M, Xu B, Durkin S, Casper A, Kastan M, Glover T. BRCA1 is required for common-fragile-site stability via its G2/M checkpoint function. Mol Cell Biol. 2004;24:6701-9 pubmed
    ..Furthermore, they suggest that mutations in BRCA1 or interacting proteins could lead to rearrangements at fragile sites in cancer cells...
  20. Semba S, Han S, Qin H, McCorkell K, Iliopoulos D, Pekarsky Y, et al. Biological functions of mammalian Nit1, the counterpart of the invertebrate NitFhit Rosetta stone protein, a possible tumor suppressor. J Biol Chem. 2006;281:28244-53 pubmed
    ..We assessed the biological effects of mammalian Nit1 expression in comparison with Fhit and observed that: 1) Nit1 expression was observed in most normal tissues and overlapped partially with Fhit ..
  21. Glover T, Hoge A, Miller D, Ascara Wilke J, Adam A, Dagenais S, et al. The murine Fhit gene is highly similar to its human orthologue and maps to a common fragile site region. Cancer Res. 1998;58:3409-14 pubmed
    The human FHIT gene is a putative tumor suppressor gene that maps to human chromosome band 3p14.2 in a region that is frequently deleted in cancers...
  22. Gaudio E, Paduano F, Spizzo R, Ngankeu A, Zanesi N, Gaspari M, et al. Fhit delocalizes annexin a4 from plasma membrane to cytosol and sensitizes lung cancer cells to paclitaxel. PLoS ONE. 2013;8:e78610 pubmed publisher
    b>Fhit protein is lost or reduced in a large fraction of human tumors, and its restoration triggers apoptosis and suppresses tumor formation or progression in preclinical models...
  23. Miuma S, Saldivar J, Karras J, Waters C, Paisie C, Wang Y, et al. Fhit deficiency-induced global genome instability promotes mutation and clonal expansion. PLoS ONE. 2013;8:e80730 pubmed publisher
    Loss of Fhit expression, encoded at chromosome fragile site FRA3B, leads to increased replication stress, genome instability and accumulation of genetic alterations...
  24. Fujishita T, Doi Y, Sonoshita M, Hiai H, Oshima M, Huebner K, et al. Development of spontaneous tumours and intestinal lesions in Fhit gene knockout mice. Br J Cancer. 2004;91:1571-4 pubmed
    The fragile histidine triad (FHIT) gene is frequently inactivated in various types of tumours. However, the system-wide pathology caused by FHIT inactivation has not been examined in detail...
  25. Durkin S, Ragland R, Arlt M, MULLE J, Warren S, Glover T. Replication stress induces tumor-like microdeletions in FHIT/FRA3B. Proc Natl Acad Sci U S A. 2008;105:246-51 pubmed
    ..The fragile site FRA3B, which lies within the FHIT tumor-suppressor gene, is a site of frequent heterozygous and homozygous deletions in many cancer cells and ..
  26. Balansky R, D Agostini F, Ganchev G, Izzotti A, Di Marco B, Lubet R, et al. Influence of FHIT on benzo[a]pyrene-induced tumors and alopecia in mice: chemoprevention by budesonide and N-acetylcysteine. Proc Natl Acad Sci U S A. 2006;103:7823-8 pubmed
    The FHIT gene has many hallmarks of a tumor-suppressor gene and is involved in a large variety of cancers...
  27. Hosseini S, Horton S, Saldivar J, Miuma S, Stampfer M, Heerema N, et al. Common chromosome fragile sites in human and murine epithelial cells and FHIT/FRA3B loss-induced global genome instability. Genes Chromosomes Cancer. 2013;52:1017-29 pubmed publisher
    ..Since we have reported that loss of expression of the FRA3B-encoded FHIT protein causes increased replication stress-induced DNA damage, we also examined the effect of FHIT-deficiency on ..
  28. Romero I, Martinez M, Garrido C, Collado A, Algarra I, Garrido F, et al. The tumour suppressor Fhit positively regulates MHC class I expression on cancer cells. J Pathol. 2012;227:367-79 pubmed publisher
    ..The other two genes, AP-2? and Fhit tumour suppressors, were studied by using siRNA to silence their expression in a MHC-I-positive metastatic cell ..
  29. Hu B, Han S, Wang X, Ottey M, Potoczek M, Dicker A, et al. Involvement of the Fhit gene in the ionizing radiation-activated ATR/CHK1 pathway. J Cell Physiol. 2005;202:518-23 pubmed
    Fragile Histidine Triad (Fhit) gene deletion, methylation, and reduced Fhit protein expression occur in about 70% of human epithelial tumors and, in some cancers, are clearly associated with tumor progression...