mTOR/S6K1 and MAPK/RSK signaling pathways coordinately regulate estrogen receptor a serine 167 phosphorylation

作者：Yamnik Rachel L; Holz Marina K^*

来源：FEBS Letters, 2010, 584(1): 124-128.

DOI：10.1016/j.febslet.2009.11.041

• p70 S6 kinase 1
• p90 ribosomal S6 kinase
• Mammalian target of rapamycin
• Rapamycin
• Estrogen receptor alpha
• Breast cancer

Resistance to anti-estrogen therapy is a major clinical concern in treatment of breast cancer. Estrogen-independent phosphorylation of estrogen receptor alpha, specifically on Ser167, is one of the contributing causes to development of resistance, and a prognostic marker for the disease. Here, we dissect the signaling pathways responsible for Ser167 phosphorylation. We report that the mTOR/S6K1 and MAPK/RSK contribute non-overlapping inputs into ER alpha activation via Ser167 phosphorylation. This cooperation may be targeted in breast cancer treatment by a combination of mTOR and MAPK inhibitors.

• 出版日期2010-1-4