Estrogen Metabolism in Endometrial Cancer. 17beta-Hydroxysteroid Dehydrogenases: New Anti-Estrogenic Therapeutics for Endometrial Cancer?

Abstract

Endometrial cancer (EC) is the most common type of uterine cancer in Western Europe. The exact cause is unknown. Excessive exposure to increased levels of unopposed estrogens is considered to play an important role. Previous studies indicate that 17'-HSDs, converting E1 to E2 and vice versa, contributes to the availability of E2. Still it is not known which of the different 17'-HSDs are responsible for the high E2 concentration in EC tissue. Therefore, we hypothesized that 17'-HSDs are aberrantly expressed in EC, which leads to a hyper-estrogenic environment. We found a significant increase in 17'-HSD1 gene expression in EC tissue. In vitro over-expression of 17'-HSD1 significantly induced conversion of E1 to E2, increasing E2 availability. This was supported by the increased cell proliferation when over-expressing 17'-HSD1 in vitro. These observations support our hypothesis. We confirmed an aberrant 17'-HSD1 expression in EC tissue and in vitro this led to increased levels of E2.