| Summary |
Each year in the Unites States, over 40,000 women die from breast cancer. The development of resistance by some breast cells to a wide variety of chemotherapeutic agents poses a major obstacle in the successful treatment of breast cancer. Because of drug resistance (DR), many of the current therapies are failing. The search for proteins responsible for this DR phenotype has implicated the anti-apoptotic protein Bcl-2, among others. It is widely accepted that when overexpressed, Bcl-2 exhibits anti-apoptotic effects. This implies that Bcl-2 regulates the normal pathway leading to programmed cell death. This study investigates the responses of both the human breast cancer cell line MCF-7 and the transfected MCF/Bcl-2 cells, overexpressing Bcl-2, to the chemotherapeutic agent, doxorubicin (Adriamycin[trademark]). The goal of this research is to examine whether cells overexpressing Bcl-2 display delayed or significantly reduced apoptosis in response to doxorubicin (DOX). In addition, subclones of the MCF/Bcl-2 pool were examined to determine their sensitivity to DOX as well as their levels of Bcl-2 expression. A correlation was found between increased resistance to DOX and increased Bcl-2 protein expression. Because the multi-drug resistance pump has been shown to confer DR in some cell lines, its expression was also assessed and found to be absent. Moreover, both Bcl-2 and multi-drug resistant-1 protein (mdr-1) expression were assessed in cells possessing an activated Raf-1 kinase which also exhibited DR. Though no upregulation of Bcl-2 was found, upregulation of mdr-1, coding for P-glycoprotein (P-gp), was observed in these cells suggesting P-gp as a means of DR. |
