BTG1, a Novel Mediator of Chemosensitivity in Breast Cancer
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2006
- Accession Number
- ADA456457
Entities
People
- Rita Nahta
Organizations
- The University of Texas MD Anderson Cancer Center