| RRC ID |
44799
|
| 著者 |
Cheng JC, Chang HM, Qiu X, Fang L, Leung PC.
|
| タイトル |
FOXL2-induced follistatin attenuates activin A-stimulated cell proliferation in human granulosa cell tumors.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
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.
|
| 巻・号 |
443(2)
|
| ページ |
537-42
|
| 公開日 |
2014-1-10
|
| DOI |
10.1016/j.bbrc.2013.12.010
|
| PII |
S0006-291X(13)02066-4
|
| PMID |
24332943
|
| MeSH |
Activins / metabolism*
Cell Proliferation
Down-Regulation
Follistatin / metabolism*
Forkhead Box Protein L2
Forkhead Transcription Factors / metabolism*
Gene Expression Regulation, Neoplastic*
Granulosa Cell Tumor
Humans
|
| IF |
2.985
|
| 引用数 |
15
|
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
KGN(RCB1154) |
