SOX9 elevation in the prostate promotes proliferation and cooperates with PTEN loss to drive tumor formation Academic Article uri icon

Overview

MeSH Major

  • Cell Proliferation
  • PTEN Phosphohydrolase
  • Prostatic Neoplasms
  • SOX9 Transcription Factor

abstract

  • Dysregulation of tissue development pathways can contribute to cancer initiation and progression. In murine embryonic prostate epithelia, the transcription factor SOX9 is required for proper prostate development. In this study, we examined a role for SOX9 in prostate cancer in mouse and human. In Pten and Nkx3.1 mutant mice, cells with increased levels of SOX9 appeared within prostate epithelia at early stages of neoplasia, and higher expression correlated with progression at all stages of disease. In transgenic mice, SOX9 overexpression in prostate epithelia increased cell proliferation without inducing hyperplasia. In transgenic mice that were also heterozygous for mutant Pten, SOX9 overexpression quickened the induction of high-grade prostate intraepithelial neoplasia. In contrast, Sox9 attenuation led to a decrease proliferating prostate epithelia cells in normal and homozygous Pten mutant mice with prostate neoplasia. Analysis of a cohort of 880 human prostate cancer samples showed that SOX9 expression was associated with increasing Gleason grades and higher Ki67 staining. Our findings identify SOX9 as part of a developmental pathway that is reactivated in prostate neoplasia where it promotes tumor cell proliferation.

publication date

  • February 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3083842

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-09-2370

PubMed ID

  • 20103652

Additional Document Info

start page

  • 979

end page

  • 87

volume

  • 70

number

  • 3