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Investigation of peroxisome proliferator-activated receptor-gamma gene Pro12Ala polymorphism and its effect on peroxisome proliferator-activated receptor-gamma mRNA expression in human cancer cell lines

Hatice Kurnaz, Gunnur Demircan, Ayyub Ebrahimi, Hande Kocak.


Abstract

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.

Key words: Peroxisome proliferator-activated receptor-gamma, Pro12Ala Polymorphism, Cancer, Cell line, Peroxisome proliferator-activated receptor-gamma mRNA expression






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