The Role of the Prohibitin Gene in Apoptosis of Breast Cancer Cells
Abstract
Prohibitin, a potential tumor suppressor protein, was originally identified by its ability to induce Gl/S arrest in human fibroblasts. Mutations in the prohibitin gene were subsequently found in sporadic breast tumors. Our experiments in B cells and breast cancer cells suggest that prohibitin protects against apoptosis induced by camptothecin, a topoisomerase I inhibitor. A human B cell line (Ramos) stably over-expressing prohibitin and treated with camptothecin exhibits 50% less apoptosis compared to the parental cell line. BT 549 breast cancer cells, which express high levels of endogenous prohibitin, exhibit 20% less death from camptothecin than ZR 751 cells, which have low levels. E2F transcriptional activity increases in response to camptothecin, but this increase is attenuated in cells overexpressing prohibitin. Moreover, we find that prohibitin and p33 associate in vitro and co-localize in the breast cancer cell lines MCF7 and T47D. Functionally, prohibitin may activate p53 mediated transcription and augment p53 binding to a target promoter. Prohibitin may intersect both the Rb/E2F and the p53 pathways, providing a link between proliferation and growth control. Our studies are elucidating the mechanisms whereby prohibitin affects the chemotherapeutic response and may help in directing therapeutic strategies for breast cancer treatment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2003
- Accession Number
- ADA424534
Entities
People
- Gina Fusaro
- Srikumar Chellappan
Organizations
- University of South Florida