{"doi":"10.1016/j.bbrc.2013.12.010","title":"FOXL2-induced follistatin attenuates activin A-stimulated cell proliferation in human granulosa cell tumors","abstract":null,"journal":"Biochemical and Biophysical Research Communications","year":2014,"id":636907,"datarank":0.48283137373023016,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"self_citation_contribution":0.48283137373023016,"citation_network_contribution":0.0,"self_endowment_contribution":0.48283137373023016,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1653479,"name":"Hsun-Ming Chang","orcid":null,"position":1,"is_corresponding":false},{"id":22193,"name":"Xin Qiu","orcid":null,"position":2,"is_corresponding":false},{"id":1653480,"name":"Lanlan Fang","orcid":null,"position":3,"is_corresponding":false},{"id":1653481,"name":"Peter C.K. Leung","orcid":null,"position":4,"is_corresponding":false},{"id":1653478,"name":"Jung-Chien Cheng","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"FOXL2-induced follistatin attenuates activin A-stimulated cell proliferation in human granulosa cell tumors","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.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24332943","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"Canadian Institutes of Health Research","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Canadian Institutes of Health Research","grant_id":"","title":null}],"total_grants":2,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"Elsevier TDM","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0006291X13020664?httpAccept=text/plain","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0006291X13020664?httpAccept=text/xml","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.bbrc.2013.12.010","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/24332943","host_type":""},{"url":"https://dx.doi.org/10.1016/j.bbrc.2013.12.010","host_type":""}],"fields_of_study":["0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Humans","Granulosa Cell Tumor","Activins","Follistatin","Cell Proliferation","Down-Regulation","Gene Expression Regulation, Neoplastic","Forkhead Transcription Factors","Forkhead Box Protein L2"],"keywords":["Follistatin","Activin","Foxl2","Human Granulosa Cell Tumors","Forkhead Box Protein L2","Gene Expression Regulation, Neoplastic","Down-Regulation","Humans","Forkhead Transcription Factors","Activins","Cell Proliferation","Granulosa Cell Tumor"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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