Terminal Differentiation of Human Breast Cancer through PPARĪ³ Academic Article uri icon

Overview

MeSH Major

  • Breast Neoplasms
  • Gene Expression Regulation, Neoplastic
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors

abstract

  • We have previously demonstrated that PPAR gamma stimulates the terminal differentiation of adipocyte precursors when activated by synthetic ligands, such as the antidiabetic thiazolidinedione (TZD) drugs. We show here that PPAR gamma is expressed at significant levels in human primary and metastatic breast adenocarcinomas. Ligand activation of this receptor in cultured breast cancer cells causes extensive lipid accumulation, changes in breast epithelial gene expression associated with a more differentiated, less malignant state, and a reduction in growth rate and clonogenic capacity of the cells. Inhibition of MAP kinase, shown previously to be a powerful negative regulator of PPAR gamma, improves the TZD ligand sensitivity of nonresponsive cells. These data suggest that the PPAR gamma transcriptional pathway can induce terminal differentiation of malignant breast epithelial cells and thus may provide a novel, nontoxic therapy for human breast cancer.

publication date

  • February 1998

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 9660931

Additional Document Info

start page

  • 465

end page

  • 70

volume

  • 1

number

  • 3