Skip to main content
SpringerLink
Log in
Book cover

Breast Cancer pp 225–246Cite as

Biological Functions of the BRCA1 and BRCA2 Proteins

  • Chapter

Part of the book series: Contemporary Cancer Research ((CCR))

Abstract

Breast cancer is the most commonly diagnosed nondermatologic cancer in women in the United States. It is second only to lung cancer as the most frequent cause of cancer-related deaths in American women. In 1996, the American Cancer Society projected over 184,000 newly diagnosed cases of breast cancer and over 44,000 deaths secondary to invasive breast cancer (1). The average American woman has a 1:8 lifetime risk of developing breast cancer. It is undoubtedly one of the most common malignancies in the Western world, yet there is currently no cure for metastatic breast cancer. For this reason, a tremendous effort has been focused on the prevention and early diagnosis of breast cancer.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. American Cancer Society. 1996. Cancer Facts and Figures, 1996. Publication no. 5008. 96.

    Google Scholar 

  2. Hall, J. M., M. K. Lee, B. Newman, J. E. Morrow, L. A. Anderson, B. Huey, and M.-C. King. 1990. Linkage of early-onset familial breast cancer to chromosome 17g21. Science 250: 1684–1689.

    Article  PubMed  CAS  Google Scholar 

  3. Miki, Y., J. Swensen, D. Shattuck-Eidens, P. A. Futreal, K. Harshman, S. Tavtigian, Q. Liu, C. Cochran, L. M. Bennett, W. Ding, R. Bell, J. Rosenthal, C. Hussey, T. Tran, M. McClure, C. Frye, T. Hattier, R. Phelps, A. Haugen-Strano, J. Katcher, K. Yakumo, Z. Gholalmi, D. Shaffer, S. Stone, S. Bayer, C. Wray, R. Bogden, P. Dayananth, J. Ward, P. Tonin, S. Narod, P. K. Bristow, F. J. Norris, L. Helvering, P. Morrison, P. Rosteck, M. Lai, J. C. Barrett, C. Lewis, S. Neuhausen, L. Cannon-Albright, D. Goldgar, R. Wiseman, A. Kamb, and M. H. Skolnick. 1994. A strong candidate for the breast and ovarian cancer susceptibility gene BRCAI. Science 266: 66–71.

    Article  PubMed  CAS  Google Scholar 

  4. Wooster, R., S. L. Neuhausen, J. Mangion, Y. Quirk, D. Ford, N. Collins, K. Nguyen, S. Seal, T. Tran, D. Averill, P. Fields, G. Marshall, S. Narod, G. M. Lenoir, H. Lynch, J. Feunteun, P. Devilee, C. J. Cornelisse, F. H. Menko, P. A. Daly, W. Ormiston, R. McManus, C. Pye, C. M. Lewis, L. A. Cannon-Albright, J. Peto, B. A. J. Ponder, M. H. Skolnick, D. F. Easton, D. E. Goldgar, and M. R. Stratton. 1994. Localization of a breasst cancer susceptibility gene, BRCA2, to chromosome 13g12–13. Science 265: 2088–2090.

    Article  PubMed  CAS  Google Scholar 

  5. Wooster, R., G. Bignell, J. Lancaster, S. Swift, S. Seal, J. Mangion, N. Collins, S. Gregory, C. Gumbs, G. Micklem, R. Barfoot, R. Hamoudi, S. Patel, C. Rice, P. Biggs, Y. Hashim, A. Smith, F. Connor, A. Arason, J. Gudmundsson, D. Ficenec, D. Kelsell, D. Ford, P. Tonin, D. T. Bishop, N. K. Spurr, B. A. J. Ponder, R. Eeles, J. Peto, P. Devilee, C. Cornelisse, H. Lynch, S. Narod, G. Lenoir, V. Egilsson, R. B. Barkadottir, D. F. Easton, D. R. Bentley,. P. A. Futreal, A. Ashworth, and M. R. Stratton. 1995. Identification of the breast cancer susceptibility gene BRCA2. Nature (London) 378: 789–792.

    CAS  Google Scholar 

  6. Easton, D. F., D. T. Bishop, D. Ford, G. P. Crockford, and the Breast Cancer Linkage Consortium. 1993. Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. Am. J. Human Genet. 52: 678–701.

    CAS  Google Scholar 

  7. BCIC. Breast Cancer Information Core, Webmaster@nhgri.nih.gov.

    Google Scholar 

  8. Bienstock, R. J., T. Darden, R. Wiseman, L Pedersen, and J. C. Barrett. 1996. Molecular modeling of the amino-terminal zinc ring domain of BRCA1. Cancer Res. 56: 2539–2545.

    PubMed  CAS  Google Scholar 

  9. Koonin, E. V., S. F. Altschul, and P. Bork. 1996. Functional motifs. Nature Genet. 13: 266–268.

    Article  PubMed  CAS  Google Scholar 

  10. Bork, P., K. Hofmann, P. Bucher, A. F. Neuwald, S. F. Altschul,. and E. V. Koonin. 1997. A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins. FASEB J. 11: 68–76.

    CAS  Google Scholar 

  11. Callebaut, I. and J.-P. Momon. 1997. From BRCA 1 to RAP 1: a widespread BRCT module closely associated with DNA repair. FEBS Lett. 400: 25–30.

    Article  PubMed  CAS  Google Scholar 

  12. Iwabuchi, K., P. L. Bartel, B. Li, R. Marraccino, and S. Fields. 1994. Two cellular proteins that bind to wild-type but not mutant p53. Proc. Natl. Acad. Sci. USA. 91: 6098–6102.

    Article  PubMed  CAS  Google Scholar 

  13. Gayther, S. A., W. Warren, S. Mazoyer, P. A. Russell, P. A. Harrington, M. Chiano, S. Seal, R. Hamoudi, E. J. van Rensburg, A. M. Dunning, R. Love, G. Evans, D. Easton, D. Clayton, M. R. Stratton, and B. A. J. Ponder. 1995. Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype-phenotype correlation. Nature Genet. 11: 428–433.

    Article  PubMed  CAS  Google Scholar 

  14. Holt, J. T., M. E. Thompson, C. Szabo, C. Robinson-Benion, C. L. Arteaga, M.-C. King, and R. A. Jensen. 1996. Growth retardation and tumour inhibition by BRCA1. Nature Genet. 12: 298–302.

    Article  PubMed  CAS  Google Scholar 

  15. Slattery, M. L. and R. A. Kerber. 1993. A comprehensive evaluation of family history and breast cancer risk. JAMA 270: 1563–1568.

    Article  PubMed  CAS  Google Scholar 

  16. Futreal, P. A., Q. Liu, D. Shattuck-Eidens, C. Cochran, K. Harshman, S. Tavtigian, L. M. Bennett, A. Haugen-Strano, J. Swensen, Y. Miki, K. Eddington, M. McClure, C. Frye, J. Weaver-Feldhaus, W. Ding, Z. Gholami, P. Soderkvist, L. Terry, S. Jhanwar, A. Berchuck, J. D. Iglehart, J. Marks, D. G. Ballinger, J. C. Barrett, M. H. Skolnick, A. Kamb, and R. Wiseman. 1994. BRCA1 mutations in primary breast and ovarian carcinomas. Science 266: 120–122.

    Article  PubMed  CAS  Google Scholar 

  17. Colditz, G. A., W. C. Willett, D. J. Hunter, M. J. Stampfer, J. E. Manson, C. H. Hennekens, B. A. Rosner, and F. E Speizer. 1993. Family history, age, and risk of breast cancer. JAMA 270: 338–343.

    Article  PubMed  CAS  Google Scholar 

  18. Easton, D. F., D. Ford, D. T. Bishop, and the Breast Cancer Linkage Consortium. 1995. Breast and ovarian cancer incidence in BRCA1-mutation carriers. Am. J. Human Genet. 56: 265–271.

    Article  CAS  Google Scholar 

  19. Ford, D. and D. F. Easton. 1995. The genetics of breast and ovarian cancer. Br. J. Cancer 72: 805–812.

    Article  PubMed  CAS  Google Scholar 

  20. Ford, D., D. F. Easton, D. T. Bishop, S. A. Narod, D. E. Goldgar, and the Breast Cancer Linkage Consortium. 1994. Risks of cancer in BRCA1-mutation carriers. Lancet 343: 692–695.

    Article  PubMed  CAS  Google Scholar 

  21. Struewing, J. P., P. Hartge, S. Wacholder, S. M. Baker, M. Berlin, M. McAdams, M. M. Timmerman, L. C. Brody, and M. A. Tucker. 1997. The risk of cancer associated with specific mutations of BRCA 1 and BRCA2 among Ashkenazi Jews. New Engl. J. Med. 336: 1401–1408.

    Article  PubMed  CAS  Google Scholar 

  22. Claus, E. B., N. Risch, and W. D. Thompson. 1991. Genetic analysis of breast cancer in the Cancer and Steroid Hormone Study. Am. J. Human Genet. 48: 232–234.

    CAS  Google Scholar 

  23. Knudson, A. G. 1971. Mutation and cancer: statistical study of retinoblastoma. Proc. Natl. Acad. Sci. USA 68: 820–823.

    Article  PubMed  Google Scholar 

  24. Knudson, A. G. 1993. Antioncogenes and human cancer. Proc. Natl. Acad. Sci. USA 90: 10914–10921.

    Article  PubMed  CAS  Google Scholar 

  25. Riley, D. J., E. Y.-H. P. Lee, and W.-H. Lee. 1994. The retinoblastoma prtoein: more than a tumor suppressor. Annu. Rev. Cell Biol. 10: 1–29.

    Article  PubMed  CAS  Google Scholar 

  26. Sidransky, D., T. Tokino, K. Helzlsouer, B. Zehnbauer, G. Rausch, B. Shelton, L. Prestigiacomo, B. Vogelstein, and N. Davidson. 1992. Inherited p53 gene mutations in breast cancer. Cancer Res. 52: 2984–2986.

    PubMed  CAS  Google Scholar 

  27. Swift, M., D. Morrell, R. B. Massey, and C. L. Chase. 1991. Incidence of cancer in 161 families affected by ataxia-telangiectasia. New Engl. J. Med. 325: 1831–1836.

    Article  PubMed  CAS  Google Scholar 

  28. Swift, M., P. J. Reitnauer, D. Morrell, and C. L. Chase. 1987. Breast and other cancers in families with ataxia-telangiectasia. New Engl. J. Med. 316: 1289–1294.

    Article  PubMed  CAS  Google Scholar 

  29. Athma, P., R. Rappaport, and M. Swift. 1996. Molecular genotyping shows that ataxiatelangiectasia heterozygotes are predisposed to breast cancer. Cancer Genet. Cytogenet. 92: 130–134.

    Article  PubMed  CAS  Google Scholar 

  30. Wooster, R., D. Ford, J. Mangion, B. A. J. Ponder, J. Peto, D. F. Easton, and M. R. Stratton. 1993. Absence of linkage to the ataxia telangiectasia locus in familial breast cancer. Human Genet. 92: 91–94.

    Article  CAS  Google Scholar 

  31. Fitzgerald, M. G., J. M. Bean, S. R. Hegde, H. Unsal, D. J. MacDonald, D. P. Harkin, D. M. Finkelstein, K. J. Isselbacher, and D. A. Haber. 1997. Heterozygous ATM mutations do not contribute to early onset of breast cancer. Nature Genet. 15: 307–310.

    Article  PubMed  CAS  Google Scholar 

  32. Chen, L. C., W. Kurisu, B. M. Ljung, E. S. Goldman, D. Moore II, and H. S. Smith. 1992. Heterogeneity for allelic loss in human breast cancer. J. Natl. Cancer Inst. 84: 506–510.

    Article  PubMed  CAS  Google Scholar 

  33. Merajver, S. D., T. M. Pham, R. F. Caduff, M. Chen, E. L. Poy, K. A. Cooney, B. L. Weber, F. S. Collins, C. Johnston, and T. S. Frank. 1995. Somatic mutations in the BRCA1 gene in sporadic ovarian tumors. Nature Genet. 9: 439–443.

    Article  PubMed  CAS  Google Scholar 

  34. Vogelstein, B. and K. W. Kinzler. 1994. Has the breast cancer gene been found? Cell 79: 1–3.

    Article  PubMed  CAS  Google Scholar 

  35. Kainu, T., J. Kononen, O. Johansson, H. Olsson, A. Borg, and J. Isola. 1996. Detection of germline BRCA1 mutations in breast cancer patients by quantitative messenger RNA in situ hybridization. Cancer Res. 56: 2912–2915.

    PubMed  CAS  Google Scholar 

  36. Chen, Y., C.-F. Chen, D. J. Riley, D. C. Allred, P.-L. Chen, D. Von Hoff, C. K. Osborne, and W.-H. Lee. 1995. Aberrant subcellular localization of BRCA1 in breast cancer. Science 270: 789–791.

    Article  PubMed  CAS  Google Scholar 

  37. Scully, R., S. Ganesan, M. Brown, J. A. De Caprio, S. A. Cannistra, J. Feunteun, S. Schnitt, and D. M. Livingston. 1996. Location of BRCA1 in human breast and ovarian cancer cells. Science 272: 123–125.

    Article  PubMed  CAS  Google Scholar 

  38. Jensen, R. A., M. E. Thompson, T. L. Jetton, C. I Szabo, R. van der Meer, B. Helou, S. R. Tronick, D. L. Page, M.-C. King, and J. T. Holt. 1996. BRCA1 is secreted and exhibits properties of a granin. Nature Genet. 12: 303–308.

    Article  PubMed  CAS  Google Scholar 

  39. Gudas, J. M., H. Nguyen, T. Li, and K. H. Cowan. 1995. Hormone-dependent regulation of BRCA1 in human breast cancer cells. Cancer Res. 55: 4561–4565.

    PubMed  CAS  Google Scholar 

  40. Gudas, J. M., T. Li, H. Nguyen, D. Jensen, F. J. Rauscher III, and K. H. Cowan. 1996. Cell cycle regulation of BRCA1 messenger RNA in human breast epithelial cells. Cell Growth Differ. 7: 717–723.

    PubMed  CAS  Google Scholar 

  41. Rao, V. N., N. Shao, M. Ahmad, and E. S. P. Reddy. 1996. Antisense RNA to the putative tumor suppressor gene BRCA1 transforms mouse fibroblasts. Oncogene 13: 523–528.

    Google Scholar 

  42. Vaughn, J. P., P. L. Davis, M. D. Jarboe, G. Huper, A. C. Evans, R. W. Wiseman, A. Berchuck, J. D. Iglehart, P. A. Futreal, and J. R. Marks. 1996. BRCA1 expression is induced before DNA synthesis in both normal and tumor-derived breast cells. Cell Growth Differ. 7: 711–715.

    PubMed  CAS  Google Scholar 

  43. Ludwig, T., D. L. Chapman, V. E. Papaioannou, and A. Efstratiadis. 1997. Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal phenotypes of Brcal, Brca2, Brcal/Brca2, Brcal/p53, and Brca2/p53 nullizygous embryos. Genes Del. 11: 1226–1241.

    Article  CAS  Google Scholar 

  44. Chen, C.-F., S. Li, Y. Chen, P.-L. Chen, Z. D. Sharp, and W.-H. Lee. 1996. The nuclear localization sequences of the BRCA1 protein interact with the importin-a subunit of the nuclear transport signal receptor. J. Biol. Chem. 271: 32863–32868.

    Article  PubMed  CAS  Google Scholar 

  45. Chen, Y., P.-L. Chen, D. J. Riley, W.-H. Lee, D. C. Allred, and C. K. Osborne. 1996. Location of BRCA1 in human breast and ovarian cancer cells. Science 272: 125–126.

    Article  PubMed  CAS  Google Scholar 

  46. Moll, U. M., G. Riou, and A. J. Levine. 1992. Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion. Proc. Natl. Acad. Sci. USA 89: 7262–7266.

    Article  PubMed  CAS  Google Scholar 

  47. Thakur, S., H. B. Zhang, Y. Peng, H. Le, B. Carroll, T. Ward, J. Yao, L. M. Farid, F. J. Couch, R. B. Wilson, and B. L. Weber. 1997. Localization of BRCA1 and splice variant identifies the nuclear localization signal. Mol. Cell. Biol. 17: 444–452.

    PubMed  CAS  Google Scholar 

  48. Wilson, C. A., M. N. Payton, G. S. Elliott„ F. W. Buaas, E. E. Cajulis, D. Grosshans, L. Ramos, D. M. Reese, D. J. Slamon, and F. J. Calzone. 1997. Differential subcellular localization, expression and biological toxicity of BRCA1 and the splice variant BRCAI-D1 lb. Oncogene 14: 1–16.

    Article  PubMed  CAS  Google Scholar 

  49. Li, S., C.-Y. Ku, A. A. Farmer, Y. S. Cong, C.-F. Chen, and W.-H. Lee. 1998. Identification of a novel cytoplasmic protein that specifically binds to nuclear localization signal motifs. J. Biol. Chem. 273: 6183–6189.

    Article  PubMed  CAS  Google Scholar 

  50. Ghosh, S. and D. Baltimore. 1990. Activation in vitro of NF-kappa B by phosphorylation of its inhibitor I-kappa B. Nature (London) 344: 678–682.

    Article  CAS  Google Scholar 

  51. Chen, Y., A. A. Farmer, C.-F. Chen, D. C. Jones, P.-L. Chen, and W.-H. Lee. 1996. BRCA1 is a 220-kDa nuclear phosphoprotein that is expressed and phosphorylated in a cell cycle-dependent manner. Cancer Res. 56: 3168–3172.

    PubMed  CAS  Google Scholar 

  52. Lane, T. F., C. Deng, A. Elson, M. S. Lyu, C. A. Kozak, and P. Leder. 1995. Expression of Brcal is associated with terminal differentiation of ectodermally and mesodermally derived tissues in mice. Genes Del,. 9: 2712–2722.

    Article  CAS  Google Scholar 

  53. Marquis, S. T., J. V. Rajan, A. Wynshaw-Boris, J. Xu, G.-Y. Yin, K. J. Abel, B. L. Weber, and L. A. Chodosh. 1995. The developmental pattern of Brcal expression implies a role in differentiation of the breast and other tissues. Nature Genet. 11: 17–26.

    Article  PubMed  CAS  Google Scholar 

  54. Marks, J. R., G. Huper, J. P. Vaughn, P. L. Davis, J. Norris, D. P. McDonnell, R. W. Wiseman, P. A. Futreal, and J. D. Iglehart. 1997. BRCA1 expression is not directly responsive to estrogen. Oncogene 14: 115–121.

    Article  PubMed  CAS  Google Scholar 

  55. Chapman, M. S. and I. M. Verma. 1996. Transcriptional activation by BRCAI. Nature (London) 382: 678–679.

    Article  CAS  Google Scholar 

  56. Monteiro, A. N. A., A. August, and H. Hanafusa. 1996. Evidence for a transcriptional activation function of BRCA1 C-terminal region. Proc. Natl. Acad. Sci. USA 93: 13595–13599.

    Article  PubMed  CAS  Google Scholar 

  57. Wu, L. C., Z. W. Wang, J. T. Tsan, M. A. Spillman, A. Phung, X. L. Xu, M. W. Yang, L.-Y. Hwang, A. M. Bowcock, and R. Baer. 1996. Identification of a RING protein that can interact in vivo with the BRCA1 gene product. Nature Genet. 14: 430–440.

    Article  PubMed  CAS  Google Scholar 

  58. Gowen, L. C., B. L. Johnson, A. M. Latour, K. K. Sulik, and B. H. Koller. 1996. Brcal deficiency results in early embryonic lethality characterized by neuroepithelial abnormalities. Nature Genet. 12: 191–194.

    Article  PubMed  CAS  Google Scholar 

  59. Hakem, R., J. L. de la Pompa, C. Sirard, R. Mo, M. Woo, A. Hakem, A. Wakeham, J. Potter, A. Reitmair, F. Billia, E. Firpo, C. C. Hui, J. Roberts, J. Rossant, and T. W. Mak. 1996. The tumor suppressor gene Brcal is required for embryonic cellular proliferation in the mouse. Cell 85: 1009–1023.

    Article  PubMed  CAS  Google Scholar 

  60. Liu, C.-Y., A. Flesken-Nikitin, S. Li, Y. Zeng, and W.-H. Lee. 1996. Inactivation of the mouse Brcal gene leads to failure in the morphogenesis of the egg cylinder in early postimplantation development. Genes Dey. 10: 1835–1843.

    Article  CAS  Google Scholar 

  61. Liu, C.-Y. and W.-H. Lee. 1997. Unpublished results.

    Google Scholar 

  62. Scully, R., J. Chen, A. Plug, Y. Xiao, D. Weaver, J. Feuntuen, T. Ashlely, and D. M. Livingston. 1997. Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell 88: 265–275.

    Article  PubMed  CAS  Google Scholar 

  63. Malkova, A.,E. L. Ivanov, and J. E. Haber. 1996. Double-strand break repair in the absence of RAD51 in yeast: a possible role for break-induced DNA replication. Proc. Nad. Acad. Sci. USA. 93: 7131–7136.

    Article  CAS  Google Scholar 

  64. Lim, D.-S. and P. Hasty. 1996. A mutation in mouse rad51 results in an early embryonic lethal that is suppressesd by a mutation in p53. Mol. Cell. Biol. 16: 7133–7143.

    PubMed  CAS  Google Scholar 

  65. Scully, R., S. F. Anderson, D. M. Chao, W. Wei, L. Ye, R. A. Young, D. M. Livingston, and J. D. Parvin. 1997. BRCA1 is a component of the RNA polymerase II holoenzyme. Proc. Natl. Acad. Sci. USA 94: 5605–5610.

    Article  PubMed  CAS  Google Scholar 

  66. Tavtigian, S. V., J. Simard, J. Rommens, F. Couch, K. Shattuck-Eidens, S. Neuhausen, S. Merajver, S. Thorlacius, K. Offit, D. Stoppa-Lyonnet, C. Belanger, R. Bell, S. Berry, R. Bogden, Q. Chen, T. Davis, M. Dumont, C. Frye, T. Hattier, S. Jammulapati, T. Janecki, P. Jiang, R. Kehrer, J.-F. Leblanc, J. T. Mitchelll, J. McArthur-Morrison, K. Nguyen, Y. Peng, C. Samson, M. Schroeder, S. C. Snyder, L. Steele, M. Stringfellow, C. Stroup, B. Swedlund, J. Swensen, D. Teng, A. Thomas, T. Tran, T. Tran, M. Tranchant, J. Weaver-Feldhaus, A. K. C. Wong, H. Shizuya, J. E. Eyfjord, L. Cannon-Albright, F. Labrie, M. H. Skolnick, B. Weber, A. Kamb, and D. E. Goldgar. 1996. The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nature Genet. 12: 333–337.

    Article  PubMed  CAS  Google Scholar 

  67. Langston, A. A., K. E. Malone, J. D. Thompson, J. R. Daling, and E. A. Ostrander. 1996. BRCA1 mutations in a population-based sample of young women with breast cancer. New Engl. J. Med. 334: 137–142.

    Article  PubMed  CAS  Google Scholar 

  68. Fitzgerald, M. G., D. J. MacDonald, M. Krainer, I. Hoover, E. O’Neil, H. Unsal, S. SilvaArrieto, D. M. Finkelstein, P. Beer-Romero, C. Englert, D. C. Sgroi, B. L. Smith, J. W. Younger, J. E. Garber, R. B. Duda, K. A. Mayzel, K. J. Isselbacher, S. H. Friend, and D. A. Haber. 1996. Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer. New Engl. J. Med. 334: 143–149.

    Article  PubMed  CAS  Google Scholar 

  69. Krainer M., S. Silva-Arrieta, M. G. Fitzgerald, A. Shimada, C. Ishioka, R. Kanamaru, D. J. MacDonald, H. Unsal, D. M. Finkelstein, A. Bowcock, K. J. Isselbacher, and D. A. Haber. 1997. Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer. New Engl. J. Med. 336: 1461–1421.

    Article  Google Scholar 

  70. Phelan, C. M., J. M. Lancaster, P. Tonin, C. Gumbs, C. Cochran, R. Carter, P. Ghadirian, C. Perret, R. Moslehi, F. Dion, M.-C. Faucher, K. Dole, S. Karimi, W. Foulkes, H. Lounis, E. Warner, P. Goss, D. Anderson, C. Larsson, S. A. Narod, and P. A. Futreal. 1996. Mutation analysis of the BRCA2 gene in 49 site-specific breast cancer families. Nature Genet. 13: 120–122.

    Article  PubMed  CAS  Google Scholar 

  71. Rebbeck, T. R., F. J. Couch, J. Kant, K. Calzone, M. DeShano, Y. Peng, K. Chen, J. E. Garber, and B. L. Weber. 1996. Genetic heterogeneity in hereditary breast cancer: role of BRCA1 and BRCA2. Am. J. Human Genet. 59: 547–553.

    CAS  Google Scholar 

  72. Couch, F. J., L. M. Farid, M. L. Deshano, S. V. Tavtigian, K. Calzone, L. Campeau, Y. Peng, B. Bogden, Q. Chen, S. Neuhausen, D. Shattuck-Eidens, A. K. Godwin, M. Daly, D. M. Radford, S. Sedlacek, J. Rommens, J. Simard, J. Garber, S. Merajver, and B. L. Weber. 1996. BRCA2 germline mutations in male breast cancer cases and breast cancer families. Nature Genet. 13: 123–125.

    Article  PubMed  CAS  Google Scholar 

  73. Collins, N., R. McManus, R. Wooster, J. Mangion, S. Seal, S. R. Lakhani, W. Ormiston, P. A. Daly, D. Ford, D. F. Easton, and M. R. Stratton. 1995. Consistent loss of the wild type allele in breast cancers from a family linked to the BRCA2 gene on chromosome 13g1213. Oncogene 10: 1673–1675.

    PubMed  CAS  Google Scholar 

  74. Miki, Y., T. Katagiri, F. Kasumi, T. Yoshimoto, and Y. Nakamura. 1996. Mutation analysis in the BRCA2 gene in primary breast cancers. Nature Genet. 13: 245–247.

    Article  PubMed  CAS  Google Scholar 

  75. Lancaster, J. M., R. Wooster, J. Mangion, C. M. Phelan, C. Cochran, C. Gumbs, S. Seal, R. Barfoot, N. Collins, G. Bignell, S. Patel, R. Hamoudi, C. Larsson, R. W. Wiseman, A. Berchuck, J. D. Iglehart, J. R. Marks, A. Ashworth, M. R. Stratton, and P. A. Futreal. 1996. BRCA2 mutations in primary breast and ovarian cancers. Nature Genet. 13: 238–240.

    Article  PubMed  CAS  Google Scholar 

  76. Marcus, J. N., P. Watson, D. L. Page, S. A. Narod, G. M. Lenoir, P. Tonin, L. Linder-Stephenson, G. Salerno, T. A. Conway, and H. T. Lynch. 1996. Hereditary Breast Cancer. Cancer 77: 697–709.

    Article  PubMed  CAS  Google Scholar 

  77. Teng, D. H.-F., R. Bogden, J. Mitchell, M. Baumgard, R. Bell, S. Berry, T. Davis, P. C. Ha, R. Kehrer, S. Jammulapati, Q. Chen, K. Offit, M. H. Skolnick, S. V. Tavtigian, S. Jhanwar, B. Swedlund, A. K. C. Wong, and A. Kamb. 1996. Low incidence of BRCA2 mutations in breast carcinoma and other cancers. Nature Genet. 13: 241–244.

    Article  PubMed  CAS  Google Scholar 

  78. Dodson, M. K., W. A. Cliby, H.-J. Xu, K. A. DeLacey, S.-X. Hu, G. L. Keeney, J. Li, K. C. Podratz, R. B. Jenkins, and W. F. Benedict. 1994. Evidence of functional RB protein in epithelial ovarian carcinomas despite loss of heterozygosity at the RB locus. Cancer Res. 54: 610–613.

    PubMed  CAS  Google Scholar 

  79. Kim, T. K., W. F. Benedict, H.-J. Xu, S.-X. Hu, J. Gosewehr, M. Velicescu, E. Yin, J. Zheng, G. D’Ablaing, and L. Dubeau. 1994. Loss of heterozygosity on chromosome 13 is common only in the biologically more aggressive subtypes of ovarian epithelial tumors and is associated with normal retinoblastoma gene expression. Cancer Res. 54: 605–609.

    PubMed  CAS  Google Scholar 

  80. Rajan, J. V., M. Wang, S. T. Marquis, and L. A. Chodosh. 1996. Brca2 is coordinately regulated with Brcal during proliferation and differentiation in mammary epithelial cells. Proc. Natl. Acad. Sci. USA 93: 113078–13083.

    Google Scholar 

  81. Sharan, S. K., M. Morimatsu, U. Albrecht, D.-K. Lim, E. Regel, C. Dinh, A. Sands, G. Eichele, P. Hasty, and A. Bradley. 1997. Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2. Nature (London) 386: 804–810.

    Article  CAS  Google Scholar 

  82. Sharan, S. K. and A. Bradley. 1996. Brca2 is coordinately regulated with Brcal during proliferation and differentiation in mammary epithelial cells. Proc. Natl. Acad. Sci. USA 93: 13078–13083.

    Article  Google Scholar 

  83. Vaughn, J. P., F. D. Cirisano, G. Huper, A. Berchuck, P. A. Futreal, J. R. Marks, and J. D. Iglehart. Cell cycle control of BRCA2. 1996. Cancer Res. 56: 4590–4594.

    PubMed  CAS  Google Scholar 

  84. Milner, M., B. Ponder, L. Hughes-Davies, M. Seltmann, and T. Kouzarides. 1997. Transcriptional activation functions in BRCA2. Nature (London) 386: 772–773.

    Article  CAS  Google Scholar 

  85. Eisinger, F., D. Stoppa-Lyonnet, M. Longy, F. Kerangueven, T. Noguchi, C. Bailly, A. Vincent-Salomon, J. Jacquemier, D. Birnbaum, and H. Sobol. 1996. Germ line mutation at BRCA1 affects the histoprognostic grade in hereditary breast cancer. Cancer Res. 56: 471–474.

    PubMed  CAS  Google Scholar 

  86. Suzuki, A., J. L. de la Pompa, R. Hakem, A. Elia, R. Yoshida, R. Mo, H. Nishina, T. Chuang, A. Wakeham, A. Itie, W. Koo, P. Billia, A. Ho, M. Fukumoto, C. C. Hui, and T. W. Mak. 1997. Brca2 is required for embryonic cellular proliferation in the mouse. Genes Dey. 11: 1242–1252.

    Article  CAS  Google Scholar 

  87. Sobol, H., D. Stopppa-Lyonnet, B. Bressac-de-Paillerets, J.-P. Peyrat, F. Derangueven, N. Janin, T. Noguchi, F. Eisinger, J.-M. Guinebretiere, J. Jacquemier, and D. Birnbaum. 1996. Truncation at conserved terminal regions of BRCA 1 protein is associated with highly proliferating hereditary breast cancers. Cancer Res. 56: 3216–3219.

    PubMed  CAS  Google Scholar 

  88. Beckman, M. W., F. Picard, H. X. An, C. R. C. vanRoeyen, S. I. Dominik, D. S. Mosny, H. G. Schnurch, H. G. Bender, and D. Niederacher. 1996. Clinical impact of detection of loss of heterozygosity of BRCA 1 and BRCA2 markers in sporadic breast cancer. Br. J. Cancer 73: 1220–1226.

    Article  Google Scholar 

  89. Kinzler, K. W. and B. Vogelstein. 1997. Gatekeepers and caretakers. Nature (London) 386: 761–763.

    Article  CAS  Google Scholar 

  90. Lane, D. P. 1992. p53, guardian of the genome. Nature (London) 358: 15–16.

    Article  PubMed  CAS  Google Scholar 

  91. Hollstein, M., D. Sidransky, B. Vogelstein, and C. C. Harris. 1991. p53 mutations on human cancers. Science. 253: 49–53.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Helen K. Chew
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrew A. Farmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wen-Hwa Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pediatrics and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Anne M. Bowcock

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Chew, H.K., Farmer, A.A., Lee, WH. (1999). Biological Functions of the BRCA1 and BRCA2 Proteins. In: Bowcock, A.M. (eds) Breast Cancer. Contemporary Cancer Research. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-456-6_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-456-6_10

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-072-4

  • Online ISBN: 978-1-59259-456-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation