Prolactin and estradiol utilize distinct mechanisms to increase serine-118 phosphorylation and decrease levels of estrogen receptor α in T47D breast cancer cells
Prolactin and estradiol utilize distinct mechanisms to increase serine-118 phosphorylation and decrease levels of estrogen receptor α in T47D breast cancer cells
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DOI：
10.1007/s10549-009-0400-7
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发表时间：
2010-04-01
影响因子：
3.8
通讯作者：
Walker, Ameae M.
中科院分区：
文献类型：
--
作者：
Chen, YenHao;Huang, KuangTzu;Walker, Ameae M.
通过检查 PRL 对雌激素受体 (ER) 丝氨酸 118 磷酸化、ER 下调和 E2 刺激的细胞增殖的影响，探讨了乳腺癌细胞中催乳素 (PRL) 和雌二醇 (E2) 之间的潜在相互作用。 E2 和 PRL 都会导致 ER α 丝氨酸 118 磷酸化延长，但使用不同的信号通路来实现这一目的。两种激素也会降低 ER α 的量，但机制不同：对于 E2 来说，降低速度很快，是由于蛋白酶体降解造成的；而对于 PRL 来说，降低速度很慢，是由于对 ER α mRNA 水平的影响造成的。单独的 PRL 对细胞数量没有影响，但增强了响应 E2 的细胞数量的增加。这些结果首次证明了 PRL 和 E2 对 E2 效果关键参数的类似影响。这表明，在乳腺癌的自然史中，这两种激素之间存在迄今为止尚未认识到的潜在重要相互作用。
Potential interactions between prolactin (PRL) and estradiol (E2) in breast cancer cells were explored by examining the effect of PRL on estrogen receptor (ER) serine-118 phosphorylation, ER down-regulation, and E2-stimulated cell proliferation. Both E2 and PRL resulted in prolonged ER alpha serine-118 phosphorylation, but used different signaling pathways to achieve this end. Both hormones also decreased the amount of ER alpha, but the mechanisms were different: for E2, the decrease was rapid and resulted from proteasomic degradation, whereas for PRL the decrease was slow and resulted from an effect on levels of ER alpha mRNA. PRL alone had no effect on cell number, but enhanced the increase in number in response to E2. These results are the first to demonstrate similar effects of PRL and E2 on parameters considered key to E2's effects. This suggests heretofore unrecognized and potentially important interactions between these two hormones in the natural history of breast cancer.