The LATS2/KPM tumor suppressor is a negative regulator of the androgen receptor

Mark Powzaniuk1, Sheila McElwee-Witmer, Robert L Vogel

  • 1Department of Molecular Endocrinology, Merck Research Laboratories, West Point, Pennsylvania 19486-0004, USA.

Insights

The study identifies LATS2 as a novel androgen receptor (AR) interacting protein that inhibits AR-regulated gene expression. Lower LATS2 expression in prostate tumors suggests its role in prostate cancer development.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Endocrinology

Background:

  • The androgen receptor (AR) is crucial for male reproductive system development and prostate cancer.
  • AR activity is regulated by interactions with various coregulator proteins.

Purpose of the Study:

  • To identify novel AR-interacting proteins.
  • To investigate the role of LATS2 in modulating AR activity and its potential involvement in prostate cancer.

Main Methods:

  • Protein-protein interaction studies to identify LATS2 as an AR-interacting protein.
  • Functional assays to assess LATS2's effect on AR-mediated gene expression.
  • Chromatin immunoprecipitation and immunohistochemistry in prostate cancer cells and tissues.

Main Results:

  • LATS2 directly interacts with the AR ligand-binding domain.
  • LATS2 inhibits androgen-regulated gene expression, including prostate-specific antigen (PSA).
  • LATS2 expression is reduced in human prostate tumors compared to normal tissue.

Conclusions:

  • LATS2 acts as a novel AR modulator, inhibiting AR transcriptional activity.
  • Reduced LATS2 expression may contribute to prostate cancer development by affecting AR signaling.

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