Differences in protein kinase C and estrogen receptor alpha, beta expression and signaling correlate with apoptotic sensitivity of MCF-7 breast cancer cell variants

Widespread use of MCF-7 human breast cancer cells as a model system for bre ast cancer has lead to variations in these cells between different laborato ries. Although several reports have addressed these differences in terms of proliferation and estrogenic response, differences in sensitivity to apopt osis have just begun to be described. Based on the possible differences in apoptotic sensitivity that may arise due to the existence of MCF-7 cell var iants, we determined the relative sensitivity of MCF-7 cell variants from t hree established laboratories (designated M, L and N) to known inducers of apoptosis, Consistent with our previous studies we demonstrate that differe nces exist among these variants in regards to tumor necrosis factor tl (TNF )-induced cell death and inhibition of proliferation in a dose-dependent ma nner. To establish if the difference in apoptotic susceptibility was specif ic to TNF, the three MCF-7 cell variants were tested for their response to other known inducers of apoptosis: okadaic acid, staurosporine and 4-hydrox y-tamoxifen. Viability and DNA fragmentation analysis revealed a similar pa ttern of resistance to apoptosis by all agents in the MCF-7 M variant.