Protein Kinase, RSK2, A Novel Drug Target for Breast Cancer

摘要

The Ser/Thr protein kinase, RSK, is an important downstream effector of MAPK but its roles in breast cancer have not previously been examined. We have now discovered that RSK activity is essential for the growth of the human breast cancer lines, MCF-7 and MDA-MB-231. Taken together, with our observations that the levels of the RSK isoform 2 (RSK2) are higher in 50% of human breast cancers compared to normal breast tissue suggests that RsK2 is an important drug target for breast cancer. To further test this hypothesis we are developing breast cell lines, that will inducible overexpress RSK2, and transgenic mice that will overexpress RSK2 in the mammary gland. RSK inhibitors, such as Sl0101 and its analog, 3Ac-SL0101, should be useful as chemotherapeutic agents for the treatment of breast cancer. The in vivo efficacy of SL0101 and 3Ac-SL0101 to inhibit the growth of MDA-MB-231 tumors is in the process of being evaluated.