Impaired turnover of prolactin receptor contributes to transformation of human breast cells.
Impaired turnover of prolactin receptor contributes to transformation of human breast cells.
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DOI：
10.1158/0008-5472.can-08-4033
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发表时间：
2009-04-01
期刊：
影响因子：
11.2
通讯作者：
Fuchs SY
中科院分区：
文献类型：
--
作者：
Plotnikov A;Varghese B;Tran TH;Liu C;Rui H;Fuchs SY
Signaling by polypeptide hormone prolactin (PRL) is mediated by its cognate receptor (PRLr). The PRLr is commonly stabilized in human breast cancer due to decreased phosphorylation of residue Ser 349, which when phosphorylated recruits the βTrcp E3 ubiquitin ligase and facilitates PRLr degradation. Here we demonstrate that an impaired PRLr turnover results in an augmented PRL signaling and PRL-induced transcription. Human mammary epithelial cells harboring degradation-resistant PRLr display accelerated proliferation and increased invasive growth. Conversely, a decrease in PRLr levels achieved by either pharmacologic or genetic means in human breast cancer cells dramatically reduced transformation and tumorigenic properties of these cells. Consequences of alteration of PRLr turnover for homeostasis of mammary cells and development of breast cancers as well as the utility of therapies that target PRLr function in these malignancies are discussed.
