17β-Hydroxysteroid Dehydrogenase Type 2 Expression Is Induced by Androgen Signaling in Endometrial Cancer

Abstract

Endometrial cancer is one of the most common female pelvic cancers and has been considered an androgen-related malignancy. Several studies have demonstrated the anti-cell proliferative effect of androgen on endometrial cancer cells; however, the mechanisms of the anti-cancer effect of androgen remain largely unclear. 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2), which catalyzes the conversion of E2 to E1, is known to be upregulated by androgen treatment in breast cancer cells. In this study, we therefore focused on the role of androgen on estrogen dependence in endometrial cancer. Dihydrotestosterone (DHT) was found to induce 17β-HSD2 mRNA and protein expression in HEC-1B endometrial cancer cells. DHT could also inhibit cell proliferation of HEC-1B when induced by estradiol treatment. In 19 endometrioid endometrial adenocarcinoma (EEA) tissues, intratumoral DHT concentration was measured by liquid chromatography/electrospray tandem mass spectrometry and was found to be significantly correlated with 17β-HSD2 immunohistochemical status. We further examined the correlations between 17β-HSD2 immunoreactivity and clinicopathological parameters in 53 EEA tissues. 17β-HSD2 status was inversely associated with the histological grade, clinical stage, and cell proliferation marker Ki-67, and positively correlated with progesterone receptor expression. 17β-HSD2 status tended to be positively associated with androgen receptor status. In 53 EEA cases, the 17β-HSD2-positive group tended to have better prognosis than that for the negative group with respect to progression-free survival and endometrial cancer-specific survival. These findings suggest that androgen suppresses the estrogen dependence of endometrial cancer through the induction of 17β-HSD2 in endometrial cancer.

Protopanaxadiol improves endometriosis associated infertility and miscarriage in sex hormones receptors-dependent and independent manners

“…Over-expression of estrogen is required in the proliferation of endometriotic lesions. Progesterone exerts as an anti-estrogen effect in the endometrium, in the way by inducing 17β-hydroxysteroid dehydrogenase 2 (HSD17B2) to produce more estrone to weaken the effects of estrogen 40 , 41 . However, there is extremely low level of PGR in endometriotic tissue that led to progesterone resistance.…”

New Insights into Breast and Endometrial Cancers

“…Additionally, this Special Issue also reports on the search for biomarkers and prognostic factors that focus on the cancer microenvironment in breast and endometrial cancers. Recently, the significance of other hormone receptors such as AR has been clarified in endometrial and breast cancers [ 25 , 26 , 27 ]; however, various hormone-dependent mechanisms should be elucidated for new therapeutic strategies for both cancers. Database analysis and in vitro research are the most important methodologies for exploring various markers for cancer research.…”

Relaxin 2/RXFP1 Signaling Induces Cell Invasion via the β-Catenin Pathway in Endometrial Cancer

“…None of the patients received radiation therapy, hormone therapy, or chemotherapy prior to surgery. The operative treatment methods in Tohoku University Hospital were summarized in our previous study [ 50 ]. The study was approved by the Tohoku University Graduate School of Medicine Research Ethical Committee (No.…”

“…The immunoreactivities of RLN2 and RXFP1 were detected in the cytoplasm of the cancer cells. The cytoplasmic immunoreactivity was evaluated based on the methods from our previous reports [ 50 , 51 ]. For a semiquantitative evaluation of the immunohistochemistry, the intensity and areas of immunoreactivity were taken into consideration.…”