Stabilization of prolactin receptor in breast cancer cells.

  • Li Y
  • Clevenger C
  • Minkovsky N
 et al. 
  • 6

    Readers

    Mendeley users who have this article in their library.
  • N/A

    Citations

    Citations of this article.

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 (beta-TrCP) ubiquitin-protein isopeptide ligase. We report here for the first time that interaction between PRLr and beta-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.

Author-supplied keywords

  • Breast
  • Breast Neoplasms
  • Breast Neoplasms: genetics
  • Breast Neoplasms: pathology
  • Breast: cytology
  • Down-Regulation
  • Epithelial Cells
  • Epithelial Cells: physiology
  • Female
  • Humans
  • Kidney
  • Kidney: cytology
  • Phosphorylation
  • Receptors, Prolactin
  • Receptors, Prolactin: biosynthesis
  • Receptors, Prolactin: metabolism
  • Receptors, Prolactin: physiology
  • Tumor Cells, Cultured
  • Ubiquitin
  • Ubiquitin: physiology
  • beta-Transducin Repeat-Containing Proteins
  • beta-Transducin Repeat-Containing Proteins: physio

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Y Li

  • C V Clevenger

  • N Minkovsky

  • K G S Kumar

  • P N Raghunath

  • J E Tomaszewski

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free