Rodrik Vanessa, Gomes Evan, Hui Li, Rockwell Patricia, Foster David A
Department of Biological Sciences, Hunter College of The City University of New York, 695 Park Avenue, New York, NY 10021, USA.
FEBS Lett. 2006 Oct 16;580(24):5647-52. doi: 10.1016/j.febslet.2006.09.013. Epub 2006 Sep 18.
Estrogen, which has been strongly implicated in breast cancer, suppresses apoptosis in estrogen receptor (ER) positive MCF-7 breast cancer cells. Phospholipase D (PLD), which is commonly elevated in ER negative breast cancer cells, also suppresses apoptosis. Survival signals generated by both estrogen and PLD are dependent upon elevated Myc expression. We report here that estrogen- and PLD-induced increases in Myc expression are due to reduced turnover of Myc protein. Estrogen and PLD suppressed phosphorylation of Myc at Thr58--a site that targets Myc for degradation by the proteasome. The data provide a mechanism for elevated Myc expression in hormone-dependent and hormone-independent breast cancer.
雌激素与乳腺癌密切相关，它可抑制雌激素受体（ER）阳性的MCF-7乳腺癌细胞的凋亡。磷脂酶D（PLD）在ER阴性乳腺癌细胞中通常升高，它也可抑制细胞凋亡。雌激素和PLD产生的存活信号均依赖于Myc表达的升高。我们在此报告，雌激素和PLD诱导的Myc表达增加是由于Myc蛋白周转减少所致。雌激素和PLD抑制了Myc在苏氨酸58位点的磷酸化，该位点是蛋白酶体将Myc降解的靶点。这些数据为激素依赖性和激素非依赖性乳腺癌中Myc表达升高提供了一种机制。
