1. 17β-Hydroxysteroid Dehydrogenase Type 2 Expression Is Induced by Androgen Signaling in Endometrial Cancer
- Author
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Sota Tanaka, Chiaki Hashimoto, Bin Li, Kiyoshi Takagi, Zhulanqiqige Doe, Takashi Suzuki, Misaki Fue, Yasuhiro Miki, Nobuo Yaegashi, and Kiyoshi Ito
- Subjects
0301 basic medicine ,Estradiol Dehydrogenases ,lcsh:Chemistry ,0302 clinical medicine ,Hydroxysteroid dehydrogenase ,lcsh:QH301-705.5 ,Spectroscopy ,endometrioid endometrial adenocarcinoma ,Dihydrotestosterone ,General Medicine ,Middle Aged ,Computer Science Applications ,030220 oncology & carcinogenesis ,endometrial cancer ,Androgens ,Immunohistochemistry ,Female ,Carcinoma, Endometrioid ,medicine.drug ,Signal Transduction ,medicine.drug_class ,androgen ,17β-hydroxysteroid dehydrogenase type 2 ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Cell Line, Tumor ,Progesterone receptor ,medicine ,Humans ,RNA, Messenger ,Physical and Theoretical Chemistry ,Molecular Biology ,Aged ,Cell Proliferation ,business.industry ,Endometrial cancer ,Organic Chemistry ,medicine.disease ,Androgen ,Endometrial Neoplasms ,Androgen receptor ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Estrogen ,Cancer research ,business - 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.
- Published
- 2018
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