1. ¹Program of Cancer Genetics, Department of Biochemistry, Drexel University, Philadelphia, PA, USA
2. ²Cancer Biology Program, Department of Obstetrics and Gynecology, Morehouse School of Medicine, Georgia Cancer Center for Excellence, Grady Health System, Atlanta, GA, USA
3. ³Department of Pathology, Emory University, Atlanta, GA, USA
4. ⁴Science Applications International Corporation, Frederick, MD, USA
5. ⁵Department of Surgery, Morehouse School of Medicine, Georgia Cancer Center for Excellence, Grady Health System, Atlanta, GA, USA
6. ⁶Department of Gynecologic Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA

Correspondence: Professor VN Rao, Cancer Biology Program, Department of Obstetrics and Gynecology, Morehouse School of Medicine, Georgia Cancer Center for Excellence, RM 10C011, Grady Health System, 80 Jesse Hill Jr Drive, Atlanta, GA 30303-3031, USA. E-mail: vrao@msm.edu

Received 6 November 2006; Revised 15 December 2006; Accepted 6 February 2007; Published online 26 March 2007.

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 wild-type 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.