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BRCA1a has antitumor activity in TN breast, ovarian and prostate cancers

  1. Author:
    Yuli, C.
    Shao, N.
    Rao, R.
    Aysola, P.
    Reddy, V.
    Oprea-llies, G.
    Lee, L.
    Okoli, J.
    Partridge, E.
    Reddy, E. S. P.
    Rao, V. N.

  2. Author Address

    Grady Hlth Syst, Georgia Canc Ctr Excellence, Morehouse Sch Med,RM 10C011, Dept Obstet & Gynecol,Canc Biol Program, Atlanta, GA 30303 USA. Drexel Univ, Dept Biochem, Program Canc Genet, Philadelphia, PA 19104 USA. Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. Sci Applicat Int Corp, Frederick, MD USA. Grady Hlth Syst, Georgia Canc Ctr Excellence, Morehouse Sch Med, Dept Surg, Atlanta, GA USA. Univ Alabama, Ctr Comprehens Canc, Dept Gynecol Oncol, Birmingham, AL USA.;Rao, VN, Grady Hlth Syst, Georgia Canc Ctr Excellence, Morehouse Sch Med,RM 10C011, Dept Obstet & Gynecol,Canc Biol Program, 80 Jesse Hill Jr Dr, Atlanta, GA 30303 USA.;vrao@msm.edu
    1. Year: 2007
    2. Date: Sep
  2. Journal: Oncogene
    1. 26
    2. 41
    3. Pages: 6031-6037
  4. Type of Article: Article
  5. ISSN: 0950-9232
  1. Abstract:

    Breast cancer gene 1 ( BRCA1) mutations predispose women to breast and ovarian cancers and men to increased risks for prostate cancer. We have previously showed BRCA1 splice variant BRCA1a/p110 to induce apoptosis of human breast cancer cells. In the current study, stable expression of BRCA1a/p110 resulted in inhibition of growth of estrogen receptor ( ER)- positive and triple-negative ( TN) human breast, ovarian, prostate and colon cancer cells and mouse fibroblast cells. Similar to wildtype BRCA1, only those cells with wild- type Rb were sensitive to BRCA1a-induced growth suppression and the status of p53 did not affect the ability of BRCA1a to suppress growth of tumor cells. BRCA1a also significantly inhibited tumor mass in nude mice bearing human CAL- 51 TN breast cancer, ES- 2 ovarian cancer and PC- 3 prostate cancer xenografts. These results suggest that the majority of exon 11 sequences ( residues 263 - 1365) are not required for the tumor suppressor function of BRCA1 proteins. This is the first report demonstrating antitumor activity of BRCA1a in human ER- positive and TN breast, hormone-independent ovarian and prostate cancer cells. Currently, there are no effective treatments against TN breast cancers and results from these studies will provide new treatments for one of the biggest needs in breast cancer research.

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External Sources

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  2. DOI: 10.1038/sj.onc.1210420
  3. View record in Web of Science®
  4. WOS: 000249277200006

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