Effect of DNA methylation profile on OATP3A1 and OATP4A1 transcript levels in colorectal cancer.
Epidemiological studies indicate that 17β-estradiol (E2) prevents colorectal cancer (CRC). Organic anion transporting polypeptides (OATPs) are involved in the cellular uptake of various endogenous and exogenous substrates, including hormone conjugates. Because transfer of estrone sulfate (E1-S) can contribute to intra-tissue conversion of estrone to the biologically active form -E2, it is evident that the expression patterns of OATPs may be relevant to the analysis of CRC incidence and therapy. We therefore evaluated DNA methylation and transcript levels of two members of the OATP family, OATP3A1 and OATP4A1, that may be involved in E1-S transport in colorectal cancer patients. We detected a significant reduction in OATP3A1 and a significant increase in OATP4A1 mRNA levels in cancerous tissue, compared with histopathologically unchanged tissue (n=103). Moreover, we observed DNA hypermethylation in the OATP3A1 promoter region in a small subset of CRC patients and in HCT116 and Caco-2 colorectal cancer cell lines. We also observed increased OATP3A1 transcript following treatment with 5-aza-2-deoxycytidine and sodium butyrate. The OATP4A1 promoter region was hypomethylated in analyzed tissues and CRC cell lines and was not affected by these treatments. Our results suggest a potential mechanism for OATP3A1 downregulation that involves DNA methylation during colorectal carcinogenesis.
Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poland.
Agnieszka Anna
AA
Rawłuszko-Wieczorek
Department of General and Colorectal Surgery, Poznań University of Medical Sciences, Poland.
Nikodem
N
Horst
Department of General and Colorectal Surgery, Poznań University of Medical Sciences, Poland.
Karolina
K
Horbacka
Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poland.
Artur Szymon
AS
Bandura
Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poland.
Monika
M
Świderska
Department of General and Colorectal Surgery, Poznań University of Medical Sciences, Poland.
Piotr
P
Krokowicz
Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poland. Electronic address: pjagodzi@am.poznan.pl.
Paweł Piotr
PP
Jagodziński
D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D020148:Butyric Acid / Q000494:pharmacology; D018938:Caco-2 Cells; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D019175:DNA Methylation; D000077209:Decitabine; D015536:Down-Regulation; D004970:Estrone / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism
D027361:Organic Anion Transporters; D012333:RNA, Messenger; C479544:SLCO3A1 protein, human; C498174:SLCO4A1 protein, human; D020148:Butyric Acid; D004970:Estrone; D000077209:Decitabine; D001374:Azacitidine; C017296:estrone sulfate
Colorectal cancer; DNA methylation; OATP3A1; OATP4A1