ERβ inhibits cyclin dependent kinases 1 and 7 in triple negative breast cancer

Oncotarget

Full text - http://bit.ly/2mlYU6k "ER? inhibits cyclin dependent kinases 1 and 7 in triple negative breast cancer" Abstract - Triple negative breast cancer (TNBC), which comprises approximately 15% of all primary breast cancer diagnoses, lacks estrogen receptor alpha, progesterone receptor and human epidermal growth factor receptor 2 expression. However, we, and others, have demonstrated that approximately 30% of TNBCs express estrogen receptor beta (ER?), a nuclear hormone receptor and potential drug target. Treatment of ER? expressing MDA-MB-231 cells with estrogen or the ER? selective agonist, LY500307, was shown to result in suppression of cell proliferation. This inhibitory effect was due to blockade of cell cycle progression. In vivo, estrogen treatment significantly repressed the growth of ER? expressing MDA-MB-231 cell line xenografts. Gene expression studies and ingenuity pathway analysis identified a network of ER? down-regulated genes involved in cell cycle progression including CDK1, cyclin B and cyclin H. siRNA mediated knockdown or drug inhibition of CDK1 and CDK7 in TNBC cells resulted in substantial decreases in proliferation regardless of ER? expression. These data suggest that the tumor suppressive effects of ER? in TNBC result from inhibition of cell cycle progression, effects that are in part mediated by suppression of CDK1/7. Furthermore, these data indicate that blockade of CDK1/7 activity in TNBC may be of therapeutic benefit, an area of study that has yet to be explored. Facebook - http://bit.ly/2xznxjV Twitter - http://bit.ly/2xzWvsu LinkedIn - http://bit.ly/2xzJ6kc Pintrest - http://bit.ly/2xzX8SS Reddit - http://bit.ly/2hoxI0N www.Oncotarget.com