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Androgen receptor and vitamin D receptor in human ovarian cancer: Growth stimulation and inhibition by ligands
Author(s) -
Ahonen Merja H.,
Zhuang YaHua,
Aine Risto,
Ylikomi Timo,
Tuohimaa Pentti
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000401)86:1<40::aid-ijc6>3.0.co;2-e
Subject(s) - androgen receptor , stimulation , endocrinology , medicine , receptor , androgen , cancer research , biology , chemistry , cancer , prostate cancer , hormone
The data suggest that 1,25‐dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] and androgens are essential for regulation of growth and differentiation in, e.g., human reproductive tissues. We investigated the possible cross‐talk between 1,25(OH) 2 D 3 and androgens in the human ovarian cancer cell line OVCAR‐3. Our data demonstrate that 1,25(OH) 2 D 3 and androgen (dihydrotestosterone, DHT) regulate the growth of OVCAR‐3 cells. Nine days' treatment of OVCAR‐3 cells with 100 nM DHT resulted in 48% stimulation of growth, whereas growth inhibition (73%) was observed after treatment with 100 nM 1,25(OH) 2 D 3 . The combination of 1,25(OH) 2 D 3 and DHT showed that 1,25(OH) 2 D 3 clearly reduces the growth‐stimulatory effect of DHT on OVCAR‐3 cells. Moreover, Western blot analysis revealed that these cells contain receptors for 1,25(OH) 2 D 3 (VDR) and androgen (AR). Expression of VDR and AR was up‐regulated by their cognate ligands. Up‐regulation of AR by 1,25(OH) 2 D 3 and of VDR by DHT provides evidence of cross‐talk between 2 signaling pathways in OVCAR‐3 cells. We also studied the immuno‐histochemical distribution of VDRs and ARs in rat ovaries and human ovarian cancer cases. In rat ovaries, VDRs were observed mainly in granulosa and theca cells and ARs in granulosa cells and surface epithelium. In the human ovarian cancer cases studied, 43% were VDR‐positive and 64% AR‐positive. Combining the results suggests that the growth of ovarian tissue might be regulated by 1,25(OH) 2 D 3 and androgen. Int. J. Cancer 86:40–46, 2000. © 2000 Wiley‐Liss, Inc.