title: Stem cell antigen-1 deficiency enhances the chemopreventive effect of peroxisome proliferator-activated receptorγ 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 PPARγ and PTEN, and a reduction of pSer84PPARγ, pERK1/2, and PPARδ. This phenotype correlated with markedly increased sensitivity of Sca-1 null mice to PPARγ agonist GW7845 and insensitivity to PPARδ 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 PPARγ 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 PPARγ.
authors.affiliation: Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA..
authors.forename: Hongyan
authors.initials: H
authors.lastname: Yuan
authors.forename: Geeta
authors.initials: G
authors.lastname: Upadhyay
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Yin
authors.forename: Levy
authors.initials: L
authors.lastname: Kopelovich
authors.forename: Robert I
authors.initials: RI
authors.lastname: Glazer
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000950:Antigens, Ly / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010080:Oxazoles / Q000494:pharmacology; D047495:PPAR gamma / Q000378:metabolism*; D010641:Phenotype; D034622:RNA Interference; D015398:Signal Transduction; D013844:Thiazoles / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D016588:Anticarcinogenic Agents; D000950:Antigens, Ly; D000970:Antineoplastic Agents; C425931:GW 501516; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D010080:Oxazoles; D047495:PPAR gamma; D013844:Thiazoles; C401311:GW 7845; D014443:Tyrosine