Androgens in endometrial carcinoma: the killer or helper?

Wu, Xirong; Zhang, K; Zhong, X; Huo, Xiaoqing; J, Zhang; Tian, Wenyan; Yang, Xiaoqing; Zhang, Y; Wang, Y

doi:10.1007/s40618-022-01916-1

Cited by 2 publications

(3 citation statements)

References 57 publications

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“…Although there are a few contradictory reports 13 , our findings are compatible with most previous studies, indicating that AR expression is a clinical indicator of the prognosis associated with uterine endometrioid carcinoma [16][17][18] . Although these results suggest that androgen has suppressing effects on endometrial cancers, experimental validation has not been obtained 8 .…”

Section: Discussionmentioning

confidence: 84%

“…Until now, the molecular biological mechanism of the androgen/AR system for the development and progression of uterine cancer has remained unclear 7 , 8 . To the best of our knowledge, this study revealed that FOXP4 is a downstream factor of the androgen/AR system in human endometrioid cancer cells for the first time.…”

Section: Discussionmentioning

confidence: 99%

“…After menopause, the production of androgen also declines. Although details of the effects of male hormones on the uterus are still unknown, the possible involvement of androgen in the development of uterine cancer has been proposed since the androgen receptor (AR) is expressed in endometrioid carcinoma [6][7][8] . Some studies suggest an antagonistic role of androgen in the pathogenesis of endometrial carcinoma.…”

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confidence: 99%

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Androgen-responsive FOXP4 is a target for endometrial carcinoma

Kayahashi,

Hasan,

Khatun

et al. 2024

Commun Biol

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Although low estrogen is considered to suppress uterine endometrial carcinoma, the most cases occur in the postmenopausal stage. After menopause, the production of androgen level also declines. Therefore, to resolve the above enigma, we hypothesize that the postmenopausal decline of androgen is a trigger of its progression. In the present study, to validate this hypothesis, we examine the pathological roles of androgen/AR by analyzing clinical data, culturing endometrioid cancer cell lines, and using murine models. Clinical data show that androgen receptor (AR) expression and serum dihydrotestosterone (DHT) are associated with lower disease-free survival (DFS). DHT suppresses malignant behaviors in AR-transfected human endometrial cancer cells (ECC). In ovariectomized Ptenff/PRcre/+ mice, DHT decreases the proliferation of spontaneously developed murine ECC. In AR-transfected human ECC and Ptenff/PRcre/+ mice, DHT suppresses FOXP4 expression. FOXP4-overexpressed human ECC increases, while FOXP4-knocked-down ECC shows decreased malignant behaviors. DHT/AR-mediated ECC suppression is restored by FOXP4 overexpression. The high FOXP4 expression is significantly correlated with low postoperative DFS. These findings indicate that the androgen/AR system suppresses the malignant activity of endometrial carcinoma and that downstream FOXP4 is another target molecule. These findings will also impact developments in clinical approaches to elderly health.

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