Stem cell antigen-1 deficiency enhances the chemopreventive effect of peroxisome proliferator-activated receptor? activation.

ABSTRACT: Stem cell antigen-1 (Sca-1, Ly6A) is a glycerophosphatidylinositol (GPI)-anchored protein that was identified as a murine marker of bone marrow stem cells. Although Sca-1 is widely used to enrich for stem and progenitor cells in various tissues, little is known about its function and associated signaling pathways in normal and malignant cells. Here, we report that the absence of Sca-1 in the mammary gland resulted in higher levels of PPAR? and PTEN, and a reduction of pSer84PPAR?, pERK1/2, and PPAR?. This phenotype correlated with markedly increased sensitivity of Sca-1 null mice to PPAR? agonist GW7845 and insensitivity to PPAR? agonist GW501516. Reduction of Sca-1 expression in mammary tumor cells by RNA interference resulted in a phenotype similar to the Sca-1 deficient mammary gland, as evidenced by increased PPAR? expression and transcriptional activity, resulting in part from a lesser susceptibility to proteasomal degradation. These data implicate Sca-1 as a negative regulator of the tumor suppressor effects of PPAR?.

SUBMITTER: Yuan H 

PROVIDER: S-EPMC3252486 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature