Impaired turnover of prolactin receptor contributes to transformation of human breast cells. Cancer Res 2009 Apr 01;69(7):3165-72
Date
03/12/2009Pubmed ID
19276348Pubmed Central ID
PMC2664855DOI
10.1158/0008-5472.CAN-08-4033Scopus ID
2-s2.0-66149095511 (requires institutional sign-in at Scopus site) 44 CitationsAbstract
Signaling by polypeptide hormone prolactin (PRL) is mediated by its cognate receptor (PRLr). PRLr is commonly stabilized in human breast cancer due to decreased phosphorylation of residue Ser349, which when phosphorylated recruits the betaTrcp E3 ubiquitin ligase and facilitates PRLr degradation. Here, we show 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.
Author List
Plotnikov A, Varghese B, Tran TH, Liu C, Rui H, Fuchs SYMESH terms used to index this publication - Major topics in bold
BreastBreast Neoplasms
Cell Growth Processes
Cell Line, Tumor
Cell Transformation, Neoplastic
Down-Regulation
Epithelial Cells
Humans
Neoplasm Invasiveness
Phosphorylation
Prolactin
Receptors, Prolactin
Signal Transduction
