Inhibition of peroxisome proliferator-activated receptor gamma increases estrogen receptor-dependent tumor specification.

ABSTRACT: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that regulates gene transcription associated with intermediary metabolism, adipocyte differentiation, and tumor suppression and proliferation. To understand the role of PPARgamma in tumorigenesis, transgenic mice were generated with mammary gland-directed expression of the dominant-negative transgene Pax8PPARgamma. Transgenic mice were phenotypically indistinguishable from wild-type (WT) mice, but mammary epithelial cells expressed a greater percentage of CD29(hi)/CD24(neg), CK5(+), and double-positive CK14/CK18 cells. These changes correlated with reduced PTEN and increased Ras and extracellular signal-regulated kinase (ERK) and AKT activation. Although spontaneous tumorigenesis did not occur, transgenic an

SUBMITTER: Yin Y 

PROVIDER: S-EPMC3693579 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature