{"doi":"10.1210/me.2009-0302","title":"Peroxisome Proliferator-Activated Receptor γ Coactivator-1α Interacts with the Androgen Receptor (AR) and Promotes Prostate Cancer Cell Growth by Activating the AR","abstract":"<jats:title>Abstract</jats:title><jats:p>There are currently few successful therapies for castration-resistant prostate cancer (CRPC). CRPC is thought to result from augmented activation of the androgen/androgen receptor (AR) signaling pathway, which could be enhanced by AR cofactors. In this study, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) was found to be an AR cofactor. PGC-1α interacted with the N-terminal domain of AR, was involved in the N- and C-terminal interaction of AR, and enhanced the DNA-binding ability of AR to androgen-responsive elements in the prostate-specific antigen enhancer and promoter regions to increase the transcription of AR target genes. Silencing of PGC-1α suppressed cell growth of AR-expressing prostate cancer (PCa) cells by inducing cell-cycle arrest at the G1 phase, similar to inhibition of androgen/AR signaling. Furthermore, PGC-1α knock-down also suppressed cell growth in the castration-resistant LNCaP-derivatives. These findings indicate that PGC-1α is involved in the proliferation of AR-expressing PCa cells by acting as an AR coactivator. Modulation of PGC-1α expression or function may offer a useful strategy for developing novel therapeutics for PCa, including CRPC, which depends on AR signaling by overexpressing AR and its coactivators.</jats:p>","journal":"Molecular Endocrinology","year":2010,"id":23394,"datarank":3.905144205918334,"base_score":4.442651256490317,"endowment":4.442651256490317,"self_citation_contribution":0.6663976884735476,"citation_network_contribution":3.238746517444786,"self_endowment_contribution":0.6663976884735476,"citer_contribution":3.238746517444786,"corpus_percentile":null,"corpus_rank":null,"citation_count":84,"citer_count":78,"citers_with_citation_signal":72,"citers_with_endowment":72,"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":143777,"name":"Akira Yokomizo","orcid":"0000-0002-5741-6280","position":1,"is_corresponding":false},{"id":143779,"name":"Yasuhiro Tada","orcid":null,"position":2,"is_corresponding":false},{"id":143782,"name":"Junichi Inokuchi","orcid":"0000-0002-6791-905X","position":3,"is_corresponding":false},{"id":143783,"name":"Katsunori Tatsugami","orcid":null,"position":4,"is_corresponding":false},{"id":143785,"name":"Kentaro Kuroiwa","orcid":null,"position":5,"is_corresponding":false},{"id":143787,"name":"Takeshi Uchiumi","orcid":null,"position":6,"is_corresponding":false},{"id":143789,"name":"Naohiro Fujimoto","orcid":null,"position":7,"is_corresponding":false},{"id":143791,"name":"Narihito Seki","orcid":null,"position":8,"is_corresponding":false},{"id":143792,"name":"Seiji Naito","orcid":null,"position":9,"is_corresponding":false},{"id":143775,"name":"Masaki Shiota","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.442651256490317,"endowment":4.442651256490317,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19884383","pmcid":"PMC5428145","openalex_id":"https://openalex.org/W2078616556","authors":[],"funders":[],"total_grants":0,"fwci":2.8743,"citation_percentile":0.90985176,"influential_citations":2,"citation_trend":[{"year":2012,"count":9},{"year":2013,"count":6},{"year":2014,"count":2},{"year":2015,"count":3},{"year":2016,"count":8},{"year":2017,"count":2},{"year":2018,"count":4},{"year":2019,"count":5},{"year":2020,"count":6},{"year":2021,"count":4},{"year":2022,"count":6},{"year":2023,"count":6},{"year":2024,"count":6},{"year":2025,"count":5}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://academic.oup.com/mend/article-pdf/24/1/114/10735523/mend0114.pdf","host_type":"journal"},{"url":"https://academic.oup.com/mend/article-pdf/24/1/114/10735523/mend0114.pdf","host_type":"BRONZE"},{"url":"https://academic.oup.com/mend/article-pdf/24/1/114/10735523/mend0114.pdf","host_type":"publisher"},{"url":"http://academic.oup.com/mend/article-pdf/24/1/114/10735523/mend0114.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1210/me.2009-0302","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19884383","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5428145","host_type":"repository"}],"fields_of_study":["Peroxisome Proliferator-Activated Receptors","Prostate Cancer Treatment and Research","Adipose Tissue and Metabolism","Biology","Medicine","Androgens","Cell Line, Tumor","Cell Proliferation","DNA-Binding Proteins","Enhancer Elements, Genetic","G1 Phase","Gene Expression Regulation, Neoplastic","Gene Knockdown Techniques","Heat-Shock Proteins","Humans","Immobilized Proteins","Male","Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha","Promoter Regions, Genetic","Prostate-Specific Antigen","Prostatic Neoplasms","Protein Interaction Domains and Motifs","RNA, Messenger","RNA, Small Interfering","Receptors, Androgen","Transcription Factors","Transcriptional Activation"],"mesh_terms":["Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha","Androgens","DNA-Binding Proteins","Enhancer Elements, Genetic","Heat-Shock Proteins","Humans","Male","Promoter Regions, Genetic","Prostatic Neoplasms","Receptors, Androgen","RNA, Messenger","Transcription Factors","Transcriptional Activation","Gene Expression Regulation, Neoplastic","G1 Phase","Prostate-Specific Antigen","RNA, Small Interfering","Cell Line, Tumor","Cell Proliferation","Protein Interaction Domains and Motifs","Immobilized Proteins","Gene Knockdown Techniques"],"keywords":["Androgen receptor","Biology","Coactivator","Prostate cancer","Cancer research","Receptor","Peroxisome proliferator-activated receptor","Nuclear receptor coactivator 3","Cell growth","Endocrinology","Internal medicine","Cancer","Transcription factor","Biochemistry","Genetics","Gene"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T19:22:01.331437Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}