Impaired turnover of prolactin receptor contributes to transformation of human breast cells

Alexandr Plotnikov, Bentley Varghese, Thai H. Tran, Chengbao Liu, Hallgeir Rui, Serge Y. Fuchs

Research output: Contribution to journalArticle

Abstract

Signaling by polypeptide hormone prolactin (PRL) is mediated by its cognate receptor (PRLr). FRLr is commonly stabilized in human breast cancer due to decreased phosphorylation of residue Ser349, which when phosphorylated recruits the ßTrcp 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 ammary cells and development of breast cancers, as well as the utility of therapies that target PRLr function in these malignancies, are discussed.

Original languageEnglish (US)
Pages (from-to)3165-3172
Number of pages8
JournalCancer Research
Volume69
Issue number7
DOIs
StatePublished - Apr 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Plotnikov, A., Varghese, B., Tran, T. H., Liu, C., Rui, H., & Fuchs, S. Y. (2009). Impaired turnover of prolactin receptor contributes to transformation of human breast cells. Cancer Research, 69(7), 3165-3172. https://doi.org/10.1158/0008-5472.CAN-08-4033