Stabilization of prolactin receptor in breast cancer cells

Y. Li, C. V. Clevenger, N. Minkovsky, Kgs Kumar, P. N. Raghunath, J. E. Tomaszewski, V. S. Spiegelman, S. Y. Fuchs

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

The role of the hormone prolactin (PRL) in the pathogenesis of breast cancer is mediated by its cognate receptor (PRLr). Ubiquitin-dependent degradation of the PRLr that negatively regulates PRL signaling is triggered by PRL-mediated phosphorylation of PRLr on Ser349 followed by the recruitment of the beta-transducin repeats-containing protein (β-TrCP) ubiquitin-protein isopeptide ligase. We report here for the first time that interaction between PRLr and β-TrCP is less efficient in human breast cancer cells than in non-tumorigenic human mammary epithelial cells. Furthermore, we demonstrate that both PRLr degradation and PRLr phosphorylation on Ser349 are impaired in breast tumor cells and tissues, an observation that directly correlates with enhanced expression of the PRLr in malignant breast epithelium. These findings represent a novel mechanism through which altered PRLr stability may directly influence the pathogenesis of breast cancer.

Original languageEnglish (US)
Pages (from-to)1896-1902
Number of pages7
JournalOncogene
Volume25
Issue number13
DOIs
StatePublished - Mar 23 2006

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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