Control of prostate cell growth: BMP antagonizes androgen mitogenic activity with incorporation of MAPK signals in Smad1

Academic Article

Abstract

  • Alterations in the signaling pathways of bone morphogenetic proteins (BMPs) and activation of the ERK/MAP kinase (MAPK) pathway by growth factors have been implicated in the development and progression of prostate cancer. Smad1 acts as a substrate for MAPKs and also performs a central role in transmitting signals from BMPs. We found that BMPs/Smad1 signaling inhibits the growth of androgen-sensitive prostate cancer cells. Upon the incorporation of ERK/MAPK signals at its linker region, Smad1 physically interacts with androgen-activated androgen receptor (AR) and suppresses its functions. BMPs induce the function of Smad1 as an AR transcriptional corepressor. We demonstrated in vivo that Smad1 signaling is low in androgen-regulated growth of prostate cancer, is activated after castration, and also is decreased in hormone-independent tumors. The activation status of ERK/MAPK parallels Smad1 in the progression of prostate cancer; thus, our findings indicate a molecular basis for the integration of signals of MAPK and Smad1 in the progression and androgen regulation of prostate cancer. © 2007 European Molecular Biology Organization | All Rights Reserved.
  • Digital Object Identifier (doi)

    Author List

  • Qiu T; Grizzle WE; Oelschlager DK; Shen X; Cao X
  • Start Page

  • 346
  • End Page

  • 357
  • Volume

  • 26
  • Issue

  • 2