Department of Biology, Stern College for Women of Yeshiva University, New York, NY 10016, USA.
FEBS Lett. 2010 Jan 4;584(1):124-8. doi: 10.1016/j.febslet.2009.11.041.
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 ERalpha activation via Ser167 phosphorylation. This cooperation may be targeted in breast cancer treatment by a combination of mTOR and MAPK inhibitors.
抗雌激素治疗耐药是乳腺癌治疗中的一个主要临床关注点。雌激素受体α的雌激素非依赖性磷酸化，特别是丝氨酸 167 的磷酸化，是导致耐药性发展的原因之一，也是该疾病的预后标志物。在这里，我们剖析了导致丝氨酸 167 磷酸化的信号通路。我们报告称，mTOR/S6K1 和 MAPK/RSK 通过丝氨酸 167 磷酸化，为 ERalpha 的激活提供非重叠的输入。通过联合使用 mTOR 和 MAPK 抑制剂，这种合作可能成为乳腺癌治疗的靶点。
