Survival Pathways and Apoptosis of Breast Cancer Cells as Targets for Therapeutic Modulation

摘要

One goal this research project has been to assess the dependence of breast cancer cell survival on the P13 kinase/Akt signaling pathway. This signaling pathway is hypothesized to be critical to breast cancer survival especially under growth-limiting conditions or when chemotherapeutics are present. Using a series of six breast cancer cell lines and a phenotypcially normal, but immortal, breast line I first determined the baseline level of phosphorylated Akt as an indicator of basal P13 kinase signaling. Phosphorylated ERKl/2 was also measured to determine if basal survival signaling through the MEKl/2-ERKl/2 pathway was occurring. While all of the breast cancer cell lines expressed basal levels of phosphorylated ERKl/2, phosphorylated Akt was only found in a fraction of the cell lines. The removal of exogenous growth factors by culture in serum-free media did not significantly change the detected level of phosphorylated Akt and ERKl/2 expressed by the cells, suggesting that P13 kinase-Akt and MEKl/2-ERKl/2 signaling occurs in the absence of exogenous growth factors. Pharmacological inhibitors of these key survival signaling pathways were tested for their affects on breast cancer cell survival under both serum- free and serum-containing conditions. Interestingly, the results to date suggest that most breast cancer cell lines rely more heavily on the MEKl/2-ERKl/2 signaling pathway than on the P13-kinase-Akt pathway for survival.