FOXL2-induced follistatin attenuates activin A-stimulated cell proliferation in human granulosa cell tumors
FOXL2-induced follistatin attenuates activin A-stimulated cell proliferation in human granulosa cell tumors
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DOI：
10.1016/j.bbrc.2013.12.010
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发表时间：
2014-01-10
影响因子：
3.1
通讯作者：
Leung, Peter C. K.
中科院分区：
文献类型：
--
作者：
Cheng, Jung-Chien;Chang, Hsun-Ming;Leung, Peter C. K.
Human granulosa cell tumors (GCTs) are rare, and their etiology remains largely unknown. Recently, the FOXL2 402C > G (C134W) mutation was found to be specifically expressed in human adult-type GCTs; however, its function in the development of human GCTs is not fully understood. Activins are members of the transforming growth factor-beta superfamily, which has been shown to stimulate normal granulosa cell proliferation; however, little is known regarding the function of activins in human GCTs. In this study, we examined the effect of activin A on cell proliferation in the human GCT-derived cell line KGN. We show that activin A treatment stimulates KGN cell proliferation. Treatment with the activin type I receptor inhibitor SB431542 blocks activin A-stimulated cell proliferation. In addition, our results show that cyclin D2 is induced by treatment with activin A and is involved in activin A-stimulated cell proliferation. Moreover, the activation of Smad signaling is required for activin A-induced cyclin D2 expression. Finally, we show that the overexpression of the wild-type FOXL2 but not the C134W mutant FOXL2 induced follistatin production. Treatment with exogenous follistatin blocks activin A-stimulated cell proliferation, and the overexpression of wild-type FOXL2 attenuates activin A-stimulated cell proliferation. These results suggest that FOXL2 may act as a tumor suppressor in human adult-type GCTs by inducing follistatin expression, which subsequently inhibits activin-stimulated cell proliferation. (C) 2013 Elsevier Inc. All rights reserved.
