Cyclin E overexpression enhances cytokine-mediated apoptosis in MCF7 breast cancer cells

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Abstract
Cyclin E, the regulatory component of the cyclin E/cyclin-dependent kinase (CDK) complex, is required for proliferation and overexpression of this cyclin is associated with many types of human tumors. To elucidate the mechanism by which cyclin E overexpression promotes tumorigenesis, cyclin E was overexpressed in two breast cancer lines: MCF7 and T47D. Cells overexpressing cyclin E display a marked decrease in the expression of Bcl-2, an antiapoptotic protein, and increased levels of the proapoptotic proteins Bad and Bax. The levels of Bcl-XL and Mcl-1 remain unchanged. Since the homeostasis of pro- and antiapoptotic proteins was altered, we asked if cyclin E overexpression modifies responses to cytokines. MCF7 cyclin E overexpressing cells have an enhanced sensitivity to Fas, TRAIL, and TNF-α-induced apoptosis. T47D cells overexpressing cyclin E have a significant increase in TNF-α and TRAIL-induced apoptosis. In conclusion, our results provide a link between expression of cyclin E, deregulation of Bcl-2, and an altered response to cytokine-mediated apoptosis.