Ligand activation of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) inhibits cell growth in a mouse mammary gland cancer cell line.
The effects of ligand activation of PPARbeta/delta were examined in the mouse mammary tumor cell line (C20). Expression of PPARbeta/delta was markedly lower in C20 cells as compared to the human non-tumorigenic mammary gland derived cell line (MCF10A) and mouse keratinocytes. Ligand activation of PPARbeta/delta in C20 cells caused upregulation of the PPARbeta/delta target gene angiopoietin-like 4 (Angptl4). Inhibition of C20 cell proliferation and clonogenicity was observed following treatment with GW0742 or GW501516, two highly specific PPARbeta/delta ligands. In addition, an increase in apoptosis was observed in C20 cells cultured with 10microM GW501516 that preceded the observed inhibition of cell proliferation. Results from this study show that proliferation of the C20 mouse mammary gland cancer cell line is inhibited by ligand activation of PPARbeta/delta due in part to increased apoptosis.
Foreman
Jennifer E
JE
Department of Veterinary and Biomedical Sciences and The Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, 16802, United States.
Sharma
Arun K
AK
Amin
Shantu
S
Gonzalez
Frank J
FJ
Peters
Jeffrey M
JM
D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008024:Ligands; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D047494:PPAR delta / Q000819:agonists* / Q000378:metabolism; D048068:PPAR-beta / Q000819:agonists* / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors; D014410:Tumor Stem Cell Assay; D010636:Phenols; D013438:Sulfhydryl Compounds
D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D051546:Cyclooxygenase 2; D008024:Ligands; D047494:PPAR delta; D048068:PPAR-beta; D013844:Thiazoles; C407088:Angptl4 protein, mouse; C425931:GW 501516; C479979:(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid; D010636:Phenols; D013438:Sulfhydryl Compounds