Expression of 11[beta]-hydroxysteroid dehydrogenase types 1 and 2 in colorectal cancer

• Published in: Cancer letters 2004-07, Vol.210 (1), p.95
• Main Authors: Zbánková, Sárka, Bryndová, Jana, Kment, Milan, Pácha, Jiri
• Format: Article
• Language: English
• Subjects: Cell culture; Colon; Colorectal cancer; Dehydrogenases; Derivatives; Enzymes; Rodents; Steroids; Tumorigenesis; Tumors
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2003.12.019

Glucocorticoid hormones have been reported to operate as regulators of cell proliferation and differentiation and to inhibit growth of several colon tumors and adenocarcinoma cell lines. The glucocorticoid action is regulated, in part, at the pre-receptor level through the expression of isoforms of 11β-hydroxysteroid dehydrogenase (11βHSD1, 11βHSD2) which are responsible for the interconversion of hormonally active cortisol to cortisone. Since both of these isoforms are expressed in the mammalian colon, we examined whether 11βHSD1 and 11βHSD2 are expressed in human colorectal cancer and whether their expression differs between neoplastic and autologous non-neoplastic tissue. We provide evidence that both isoforms of 11βHSD are expressed in the colon adenocarcinoma, but their expression is not identical in neoplastic and non-neoplastic tissue. There is a significant decrease of 11βHSD2 mRNA abundance and enzyme activity in neoplastic tissue. In contrast, 11βHSD1 activity and mRNA abundance are increased in some but not all tumor samples. The results demonstrate that (1) neoplastic transformation is associated with decreasing steady-state levels of 11βHSD2 mRNA and enzyme activity and in some cases also with increasing expression of 11βHSD1, and (2) colorectal tumor cells have a decreased capability of autocrine inactivation of glucocorticoids.