title: Expression of 11β-hydroxysteroid dehydrogenase type 2 is deregulated in colon carcinoma.
abstract: Although the effects of glucocorticoids on proliferation, differentiation and apoptosis are well known, and steroid hormones have been identified to play a role in pathogenesis and the development of various cancers, limited data are available regarding the relationship between the local metabolism of glucocorticoids and colorectal adenocarcinoma (CRC) formation. Glucocorticoid metabolism is determined by 11β-hydroxysteroid dehydrogenases type 1 and 2 (11HSD1, 11HSD2), which increase the local concentration of cortisol due to the reduction of cortisone, or decrease this concentration due to the oxidation of cortisol. The objective of this study was to evaluate the extent of 11HSD1 and 11HSD2 mRNA in pre-malignant colorectal polyps and in CRC. The specimens were retrieved from patients by endoscopic or surgical resection and the expression of 11HSD1 and 11HSD2 was measured by real-time PCR. The polyps were of the following histological types: hyperplastic polyps and adenomas with low- or high-grade dysplasia. The neoplastic tissue of CRC obtained during tumor surgery was also studied. It was found that 11HSD2 was not only downregulated in CRC but already in the early stages of neoplastic transformation (adenoma with low-grade dysplasia). In contrast, the level of 11HSD1 was significantly increased in CRC but not in pre-malignant polyps. The results demonstrate that the downregulation of 11HSD2 gene expression is a typical feature of the development of colorectal polypous lesions and their transformation into CRC.
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, and Second Department of Internal Medicine, Third Faculty of Medicine, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Moravec
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, and Second Department of Internal Medicine, Third Faculty of Medicine, Prague, Czech Republic.
authors.forename: Jirí
authors.initials: J
authors.lastname: Svec
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Ergang
authors.affiliation: Department of Pathology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Václav
authors.initials: V
authors.lastname: Mandys
authors.affiliation: Department of Pathology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Reháková
authors.affiliation: Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Zdena
authors.initials: Z
authors.lastname: Zádorová
authors.affiliation: Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Hajer
authors.affiliation: Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Kment
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic, and Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic. pacha@biomed.cas.cz.
authors.forename: Jirí
authors.initials: J
authors.lastname: Pácha
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000032:analysis / Q000096:biosynthesis; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000032:analysis / Q000096:biosynthesis*; D000230:Adenocarcinoma / Q000201:enzymology*; D018256:Adenomatous Polyps / Q000201:enzymology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D015179:Colorectal Neoplasms / Q000201:enzymology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D061346:Laser Capture Microdissection; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000201:enzymology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2