Transforming growth factorβ1 and epidermal growth factor decrease the expression of 17β-hydroxysteroid dehydrogenase type 2 in endometrial carcinoma cells
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Estradiol (E2) is the major molecular form of estrogens. Its biological effects are determined by estrogen receptors and intracellular E2 concentration in target cells. Regulation of intracellular E2 concentration involves the action of 17β-hydroxysteroid dehydrogenase (17HSD) type 2, the enzyme inactivating E2 to estrone. It has been demonstrated that 17HSD type 2 is expressed in normal endometrial epithelia and emdometrial carcinoma cells (RL 95-2). However, the regulatory mechanism of 17HSD type 2 expression in emdometrial cancer cells remains unknown. In the present study, the effects of transforming growth factor-β1 (TGF-β1) and epidermal growth factor (EGF) on 17HSD type 2 expression in RL 95-2 cells have been investigated using enzyme activity assay and Northern blot analysis. After stimulation with TGF-β1 or EGF, the in vivo oxidative 17HSD activity in RL 95-2 cells was significantly decreased. It appeared that the inhibitory effect of TGF-β1 and EGF on the enzyme activity of 17HSD type 2 is dose-and time-dependent. Northern blot analysis further revealed that treatment of cells for 48 h with 10 ng/mL TGF-1 β and 50 ng/mL EGF reduced the expression 17HSD type 2 mRNA to 30% and 20% of the control level, respectively. The data demonstrate that 17HSD type 2 expression in endometrial carcinoma cells is down-regulated by certain growth factors.
Keywordsendometrium estrogen 17β-hydroxysteroid dehydrogenase growth factor
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