title: Expression of 17β-hydroxysteroid dehydrogenase type 1 in gastric cancer.
abstract: There are several findings suggesting the protective role of estrogens in gastric carcinogenesis. Extragonadal 17β-estradiol (E2) may be formed during estrone (E1) reduction to E2 by 17-β-hydroxysteroid dehydrogenase type 1 (HSD17B1). Therefore, we studied the HSD17B1 transcript and protein levels in primary nontumoral and tumoral gastric tissue from the same 21 patients with gastric cancer (GC). We also assessed the effect of 5-Aza-2'-deoxycytidine (5-dAzaC), on the methylation status of HSD17B1 and its expression and conversion of E1 to E2 in HGC-27 and EPG 85-257 GC cells. We identified the presence of HSD17B1 transcript and protein in HGC-27 and EPG 85-257 GC cells as well as in primary nontumoral and tumoral tissues from patients with GC. Moreover, we found that 5-dAzaC significantly up-regulated the HSD17B1 transcript and protein levels, which is associated with increased conversion of E1 to E2 in HGC-27 and EPG 85-257 GC cells. The changes in HSD17B1 expression in both HGC-27 and EPG 85-257 cells were accompanied by 5-dAzaC induced DNA demethylation in the 5' flanking region. Our results demonstrated that HSD17B1 expression and its ability to convert the weak estrogen E1 to the more potent E2 can be associated with DNA methylation in the 5' flanking region in GC cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego St., 60-781 Poznań, Poland. Electronic address: pjagodzi@ump.edu.pl.
authors.forename: Bartosz Adam
authors.initials: BA
authors.lastname: Frycz
authors.forename: Dawid
authors.initials: D
authors.lastname: Murawa
authors.forename: Maciej
authors.initials: M
authors.lastname: Wysocki-Borejsza
authors.forename: Ryszard
authors.initials: R
authors.lastname: Marciniak
authors.forename: Paweł
authors.initials: P
authors.lastname: Murawa
authors.forename: Michał
authors.initials: M
authors.lastname: Drews
authors.forename: Paweł Piotr
authors.initials: PP
authors.lastname: Jagodziński
mesh_terms: D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D004958:Estradiol / Q000096:biosynthesis*; D004960:Estradiol Dehydrogenases / Q000378:metabolism*; D004970:Estrone / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008745:Methylation / Q000187:drug effects; D013274:Stomach Neoplasms / Q000201:enzymology*; D015854:Up-Regulation
chemical_list: D004970:Estrone; D004958:Estradiol; D000077209:Decitabine; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human; D001374:Azacitidine
keywords: 17-beta-estradiol; Gastric cancer; HSD17B1