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

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.

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Acknowledgements

We thank J Gioanne and Jean Louis Fischel of Oncopharmacologic laboratories for the CAL-51 cell line and Tyler Jacks for the p53−/− mouse embryo fibroblasts. We thank Kashwayne Williams for secretarial assistance. We also thank all the other members of Rao and Reddy labs for their help. VNR dedicates this paper to her mother Rohini N Rao. This work was funded in part by Georgia Cancer Coalition Distinguished Cancer Scholar Award, NIH Ovarian Cancer Spore grant to VN Rao and Georgia Cancer Coalition Distinguished Cancer Scholar Award to ESP Reddy. This work was supported in part by NIH-NCRR-RCMI grants G-12-RR03034 and SP20RR11104.

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Correspondence to V N Rao.

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Yuli, C., Shao, N., Rao, R. et al. BRCA1a has antitumor activity in TN breast, ovarian and prostate cancers. Oncogene 26, 6031–6037 (2007). https://doi.org/10.1038/sj.onc.1210420

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