The Peroxisome proliferator-activated receptor-gamma (PPARγ) is a member of the nuclear receptor family of transcription factors. In addition to its role in lipid and glucose metabolisms, PPARγ has possible roles in tumor suppression. One of the most common variations in PPARγ is the Pro12Ala polymorphism. It is the change of proline amino acid to alanine amino acid by the conversion of cytosin (C) to guanine (G) at 34th nucleotide of the 12th codon PPARγ gene. Several recent studies have shown that Pro12Ala polymorphism may be associated with many diseases, such as obesity, diabetes, and some types of cancer. Moreover, Pro12Ala polimorphism has been shown to affect PPARγ mRNA expression in the context of obesity. However, there have been no studies investigating the relationship Pro12Ala polymorphism and PPARγ mRNA expression in cancer. In this study, Pro12Ala polymorphism in PPARγ gene was investigated in cancer and normal cell lines via using restriction fragment length polymorphism and Sanger Sequencing. Depending on the Pro12Ala status, the effect of the polymorphism on PPARγ mRNA expression was investigated via using Real Time Polymerase Chain Reaction. In conclusion; amongst 13 cell lines that were screened, heterozygous Pro12Ala polymorphism was detected only in AGS and Caki-1 cancer cell lines. PPARγ mRNA expression in these cell lines was found to be lower than PPARγ mRNA expression in cell lines without Pro12Ala polymorphism such as MCF10A, SK-BR-3, MDA-MB-468. Taken together, Pro12Ala polymorphism may modulate the mRNA expression level of PPARγ. The role of this modulation in cancer should further be investigated.
Schoonjans K, Martin G, Staels B, et al. Peroxisome proliferator-activated receptors, orphans with ligands and functions. Curr Opin Lipidol. 1997;8:15966.
He W. PPARgamma2 polymorphism and human health. PPAR Res. 2009;2009:849538.
Aprile M, Ambrosio MR, D’Esposito V, Beguinot F, Formisano P, Costa V, et al. PPARG in Human Adipogenesis: Differential Contribution of Canonical Transcripts and Dominant Negative Isoforms. PPAR Res. 2014;2014:537865.
Gimble JM, Pighetti GM, Lerner MR, et al. Expression of peroxisome proliferator activated receptor mRNA in normal and tumorigenic rodent mammary glands. Biochem Biophys Res Commun. 1998;253:813-7.
Yen CJ, Beamer BA, Negri C, et al. Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem Biophys Res Commun. 1997;241:270-4.
Deeb SS, Fajas L, Nemoto M, et al. A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet. 1998;20:284-7.
Michalik L, Desvergne B, Wahli W. Peroxisome-proliferator-activated receptors and cancers: complex stories. Nature Reviews Cancer. 2004;4:6170.
Wei Z, Han G, Bai X. Effect of Proliferator-Activated Receptor-gamma Pro12Ala Polymorphism on Colorectal Cancer Risk: A Meta-Analysis. Med Sci Monit. 2015;21:1611-6.
Berhouma R, Kouidhi S, Ammar M, Abid H, Ennafaa H, Benammar-Elgaaied A. Correlation of peroxisome proliferator-activated receptor (PPAR-gamma) mRNA expression with Pro12Ala polymorphism in obesity. Biochem Genet. 2013;51:256-63.
10. Xita N, Lazaros L, Georgiou I, et al. The Pro12Ala polymorphism of the PPAR-gamma gene is not associated with the polycystic ovary syndrome. Hormones (Athens). 2009;8:267-72.
11. Chao CT, Chen YC, Chiang CK, et al. Interplay between Superoxide Dismutase, Glutathione Peroxidase, and Peroxisome Proliferator Activated Receptor Gamma Polymorphisms on the Risk of End-Stage Renal Disease among Han Chinese Patients. Oxid Med Cell Longev. 2016;2016:8516748.
12. Saifullah, Tsukahara T. Genotyping of single nucleotide polymorphisms using the SNP-RFLP method. Biosci Trends. 2018;12:240-6.
13. Sato H, Ishihara S, Kawashima K, et al. Expression of peroxisome proliferatoractivated receptor (PPAR)gamma in gastric cancer and inhibitory effects of PPARgamma agonists. Br J Cancer. 2000;83:1394-400.
14. Mao Q, Guo H, Gao L, et al. Peroxisome proliferator-activated receptor gamma2 Pro12Ala (rs1801282) polymorphism and breast cancer susceptibility: a meta-analysis. Mol Med Rep. 2013;8:1773-8.
15. Vogel U, Christensen J, Nexo BA, et al. Peroxisome proliferator-activated [corrected] receptor-gamma2 [corrected] Pro12Ala, interaction with alcohol intake and NSAID use, in relation to risk of breast cancer in a prospective study of Danes. Carcinogenesis. 2007;28:427-34.
16. Wu MH, Chu CH, Chou YC, et al. Joint effect of peroxisome proliferatoractivated receptor gamma genetic polymorphisms and estrogen-related risk factors on breast cancer risk: results from a case-control study in Taiwan. Breast Cancer Res Treat. 2011;127:777-84.
17. Elstner E, Muller C, Koshizuka K, et al. Ligands for peroxisome proliferatoractivated receptorgamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc Natl Acad Sci U S A. 1998;95:8806-11.