Chromatin-Associated Protein SIN3B Prevents Prostate Cancer Progression by Inducing Senescence

Cancer Res. 2017 Oct 1;77(19):5339-5348. doi: 10.1158/0008-5472.CAN-16-3410. Epub 2017 Aug 14.

Abstract

Distinguishing between indolent and aggressive prostate adenocarcinoma remains a priority to accurately identify patients who need therapeutic intervention. SIN3B has been implicated in the initiation of senescence in vitro Here we show that in a mouse model of prostate cancer, SIN3B provides a barrier to malignant progression. SIN3B was required for PTEN-induced cellular senescence and prevented progression to invasive prostate adenocarcinoma. Furthermore, SIN3B was downregulated in human prostate adenocarcinoma correlating with upregulation of its target genes. Our results suggest a tumor suppressor function for SIN3B that limits prostate adenocarcinoma progression, with potential implications for the use of SIN3B and its target genes as candidate diagnostic markers to distinguish indolent from aggressive disease. Cancer Res; 77(19); 5339-48. ©2017 AACR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Animals
  • Apoptosis
  • Cell Proliferation
  • Cellular Senescence*
  • Chromatin / metabolism
  • Disease Models, Animal*
  • Disease Progression
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • PTEN Phosphohydrolase / physiology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Repressor Proteins / physiology*
  • Tumor Cells, Cultured

Substances

  • Chromatin
  • Repressor Proteins
  • SIN3B protein, human
  • Sin3b protein, mouse
  • PTEN Phosphohydrolase