%0 Journal Article
%T Decreased expression of 17¦Â-hydroxysteroid dehydrogenase type 1 is associated with DNA hypermethylation in colorectal cancer located in the proximal colon
%A Agnieszka Raw£¿uszko
%A Karolina Horbacka
%A Piotr Krokowicz
%A Pawe£¿ Jagodzi¨½ski
%J BMC Cancer
%D 2011
%I BioMed Central
%R 10.1186/1471-2407-11-522
%X HSD17B1 expression was analyzed in colorectal cancer cell lines (HT29, SW707) and primary colonic adenocarcinoma tissues collected from fifty two patients who underwent radical colon surgical resection. Histopathologically unchanged colonic mucosa located at least 10-20 cm away from the cancerous lesions was obtained from the same patients. Expression level of HSD17B1 using quantitative PCR and western blot were evaluated. DNA methylation level in the 5' flanking region of HSD17B1 CpG rich region was assessed using bisulfite DNA sequencing and HRM analysis. The influence of DNA methylation on HSD17B1 expression was further evaluated by ChIP analysis in HT29 and SW707 cell lines. The conversion of estrone (E1) in to E2 was determined by electrochemiluminescence method.We found a significant decrease in HSD17B1 transcript (p = 0.0016) and protein (p = 0.0028) levels in colorectal cancer (CRC) from the proximal but not distal colon and rectum. This reduced HSD17B1 expression was associated with significantly increased DNA methylation (p = 0.003) in the CpG rich region located in the 5' flanking sequence of the HSD17B1 gene in CRC in the proximal but not distal colon and rectum. We also showed that 5-dAzaC induced demethylation of the 5' flanking region of HSD17B1, leading to increased occupation of the promoter by Polymerase II, and increased transcript and protein levels in HT29 and SW707 CRC cells, which contributed to the increase in E2 formation.Our results showed that reduced HSD17B1 expression can be associated with DNA methylation in the 5' flanking region of HSD17B1 in CRC from the proximal colon.Colorectal cancer (CRC) is the third in the United States [1] and second in Europe [2] cause of malignant disease deaths among adults. Population based studies have shown significant gender differences in CRC incidence and mortality [3]. CRC occurrence is more frequent among men than in pre-menopausal women, which suggests a protective role of 17-¦Â-estradiol (E2) in th
%U http://www.biomedcentral.com/1471-2407/11/522