Downregulation of estrogen-metabolizing 17 beta-hydroxysteroid dehydrogenase type 2 expression correlates inversely with Ki67 proliferation marker incolon-cancer development

The 17HSDs are a group of isozymes that catalyze the interconversion betwee n high-activity 17 beta -hydroxysteroids and low-activity 17-ketosteroids. In the present study, we characterized the expression of 17HSD types 1 and 2 in normal and malignant gastrointestinal tissues and cells. Using the col on as a model for cancer of the gastrointestinal tract, expression of the 1 7HSD enzymes in cancer development was studied and correlated with prolifer ation and differentiation markers as assessed by Ki67 and mucin staining, r espectively. In normal colon and small intestine, 17HSD type 2 mRNA was exp ressed in the surface epithelial cells and, to a lesser extent, in the cryp tal epithelial cells. In colon-cancer specimens, 17HSD type 2 expression wa s downregulated both in the tissues and in the cell lines and correlated in versely with the proliferation marker. No expression for the 17HSD type I e nzyme was observed in normal or cancerous gastrointestinal tract tissues. I n line with the expression studies, 17HSD activity measurements with colon cells showed that only the oxidative conversion of E2 to E1 was present, an d Northern blot analysis showed the signal only for 17HSD type 2. Localizat ion of the ERs alpha and beta, assessed by immunohistochemistry and in situ hybridization, showed the presence of ERP in the lamina propria of the col on. Our study shows that 17HSD type 2 expression is associated with the fun ctional integrity of the gastrointestinal tract. The decrease in expression of the type 2 enzyme may increase estrogen influence in colon cancer. (C) 2002 Wiley-Liss, Inc.