BTG1, a Novel Mediator of Chemosensitivity in Breast Cancer
Final rept. 15 Jun 2005-14 Jun 2006
M D ANDERSON CANCER CENTER HOUSTON TX
Pagination or Media Count:
The anti-apoptotic protein Bcl-2 is overexpressed in a majority of breast cancers, and is associated with a diminished apoptotic response and resistance to various anti-tumor agents. Bcl-2 inhibition is currently being explored as a possible strategy for sensitizing breast cancer cells to standard chemotherapeutic agents. Antisense AS Bcl-2 oligonucleotides represent one method for blocking the anti-apoptotic effects of Bcl-2. In this study we demonstrate that AS Bcl-2 efficiently blocks Bcl-2 expression, resulting in apoptosis of breast cancer cells. AS Bcl-2-mediated cytotoxicity was associated with induction of the B-cell translocation gene 1 BTG1. Importantly, knockdown of BTG1 reduced AS Bcl-2-mediated cytotoxicity in breast cancer cells. Further, BTG1 expression appears to be negatively regulated by Bcl-2, and exogenous expression of BTG1 induced apoptosis. These results suggest that BTG1 is a Bcl-2-regulated mediator of apoptosis in breast cancer cells, and that its induction contributes to AS Bcl-2-mediated cytotoxic effects.
- Anatomy and Physiology
- Medicine and Medical Research