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Updated: Jul 16, 2026

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
Published on: August 12, 2015
BRCA1a has antitumor activity in TN breast, ovarian and prostate cancers
1Program of Cancer Genetics, Department of Biochemistry, Drexel University, Philadelphia, PA, USA.
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.
Insights
The BRCA1a splice variant inhibits the growth of various cancer cells, including triple-negative breast cancer. This finding offers potential new treatments for difficult-to-treat cancers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Mutations in Breast Cancer gene 1 (BRCA1) increase risks for breast, ovarian, and prostate cancers.
- A previously identified BRCA1 splice variant, BRCA1a/p110, demonstrated the ability to induce apoptosis in human breast cancer cells.
Purpose of the Study:
- To investigate the tumor suppressor function of the BRCA1a/p110 splice variant.
- To evaluate the efficacy of BRCA1a/p110 in inhibiting the growth of various cancer cell types and in vivo tumor models.
Main Methods:
- Stable expression of BRCA1a/p110 in human ER-positive and triple-negative (TN) breast, ovarian, prostate, and colon cancer cells, as well as mouse fibroblast cells.
- Assessment of growth suppression in relation to wild-type Rb and p53 status.
- Evaluation of tumor growth inhibition in nude mice xenograft models (CAL-51 TN breast, ES-2 ovarian, PC-3 prostate cancer).
Main Results:
- Stable expression of BRCA1a/p110 inhibited the growth of ER-positive and TN breast, ovarian, prostate, and colon cancer cells.
- Growth suppression was dependent on wild-type Rb but independent of p53 status.
- BRCA1a significantly reduced tumor mass in xenograft models of TN breast, ovarian, and prostate cancer.
Conclusions:
- The BRCA1a/p110 splice variant exhibits significant antitumor activity across multiple cancer types, including hormone-independent ovarian and prostate cancers.
- The majority of exon 11 sequences are not essential for the tumor suppressor function of BRCA1 proteins.
- BRCA1a represents a promising therapeutic candidate for triple-negative breast cancers and other malignancies with limited treatment options.
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