{"doi":"10.1038/sj.bjc.6690684","title":"Switch from antagonist to agonist of the androgen receptor blocker bicalutamide is associated with prostate tumour progression in a new model system","abstract":null,"journal":"British Journal of Cancer","year":1999,"id":620960,"datarank":0.906750797105402,"base_score":6.045005314036012,"endowment":6.045005314036012,"self_citation_contribution":0.906750797105402,"citation_network_contribution":0.0,"self_endowment_contribution":0.906750797105402,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":421,"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":1603177,"name":"J Hoffmann","orcid":null,"position":1,"is_corresponding":false},{"id":1603179,"name":"M Erdel","orcid":null,"position":2,"is_corresponding":false},{"id":1603180,"name":"I E Eder","orcid":null,"position":3,"is_corresponding":false},{"id":1603181,"name":"A Hobisch","orcid":null,"position":4,"is_corresponding":false},{"id":1603182,"name":"A Hittmair","orcid":null,"position":5,"is_corresponding":false},{"id":1603183,"name":"G Bartsch","orcid":null,"position":6,"is_corresponding":false},{"id":1603184,"name":"G Utermann","orcid":null,"position":7,"is_corresponding":false},{"id":1603185,"name":"M R Schneider","orcid":null,"position":8,"is_corresponding":false},{"id":1603186,"name":"K Parczyk","orcid":null,"position":9,"is_corresponding":false},{"id":1603187,"name":"H Klocker","orcid":null,"position":10,"is_corresponding":false},{"id":1603176,"name":"Z Culig","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Switch from antagonist to agonist of the androgen receptor blocker bicalutamide is associated with prostate tumour progression in a new model system","abstract":"Advanced prostate cancer is treated by androgen ablation and/or androgen receptor (AR) antagonists. In order to investigate the mechanisms relevant to the development of therapy-resistant tumours, we established a new tumour model which closely resembles the situation in patients who receive androgen ablation therapy. Androgen-sensitive LNCaP cells were kept in androgen-depleted medium for 87 passages. The new LNCaP cell subline established in this manner, LNCaP-abl, displayed a hypersensitive biphasic proliferative response to androgen until passage 75. Maximal proliferation of LNCaP-abl cells was achieved at 0.001 nM of the synthetic androgen methyltrienolone (R1881), whereas 0.01 nM of this compound induced the same effect in parental cells. At later passages (> 75), androgen exerted an inhibitory effect on growth of LNCaP-abl cells. The non-steroidal anti-androgen bicalutamide stimulated proliferation of LNCaP-abl cells. AR protein expression in LNCaP-abl cells increased approximately fourfold. The basal AR transcriptional activity was 30-fold higher in LNCaP-abl than in LNCaP cells. R1881 stimulated reporter gene activity in LNCaP-abl cells even at 0.01 nM, whereas 0.1 nM of R1881 was needed for induction of the same level of reporter gene activity in LNCaP cells. Bicalutamide that acts as a pure antagonist in parental LNCaP cells showed agonistic effects on AR transactivation activity in LNCaP-abl cells and was not able to block the effects of androgen in these cells. The non-steroidal AR blocker hydroxyflutamide exerted stimulatory effects on AR activity in both LNCaP and LNCaP-abl cells; however, the induction of reporter gene activity by hydroxyflutamide was 2.4- to 4-fold higher in the LNCaP-abl subline. The changes in AR activity were associated neither with a new alteration in AR cDNA sequence nor with amplification of the AR gene. Growth of LNCaP-abl xenografts in nude mice was stimulated by bicalutamide and repressed by testosterone. In conclusion, our results show for the first time that the nonsteroidal anti-androgen bicalutamide acquires agonistic properties during long-term androgen ablation. These findings may have repercussions on the natural course of prostate cancer with androgen deprivation and on strategies of therapeutic intervention.","is_dataset_classified":null,"base_score":6.045005314036012,"endowment":6.045005314036012,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10496349","pmcid":"PMC2362859","openalex_id":"https://openalex.org/W2095873383","authors":[],"funders":[],"total_grants":0,"fwci":7.3241,"citation_percentile":0.97682613,"influential_citations":0,"citation_trend":[{"year":2012,"count":25},{"year":2013,"count":22},{"year":2014,"count":19},{"year":2015,"count":16},{"year":2016,"count":21},{"year":2017,"count":18},{"year":2018,"count":14},{"year":2019,"count":18},{"year":2020,"count":15},{"year":2021,"count":19},{"year":2022,"count":16},{"year":2023,"count":16},{"year":2024,"count":13},{"year":2025,"count":10},{"year":2026,"count":1}],"oa_status":"hybrid","license":"cc-by-nc-sa","oa_locations":[{"url":"https://www.nature.com/articles/6690684.pdf","host_type":"journal"},{"url":"https://www.nature.com/articles/6690684.pdf","host_type":"publisher"},{"url":"http://www.nature.com/articles/6690684.pdf","host_type":"publisher"},{"url":"http://www.nature.com/articles/6690684","host_type":"publisher"},{"url":"https://doi.org/10.1038/sj.bjc.6690684","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10496349","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2362859","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC2362859","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC2362859?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Prostate Cancer Treatment and Research","Hormonal and reproductive studies","Sexual Differentiation and Disorders"],"mesh_terms":["Androgen Antagonists","Androgens","Anilides","Animals","Antineoplastic Agents","Cell Division","Humans","Ligands","Male","Neoplasm Transplantation","Neoplasms, Hormone-Dependent","Nitriles","Prostatic Neoplasms","Receptors, Androgen","RNA, Messenger","Tosyl Compounds","Transcription, Genetic","Tumor Cells, Cultured","Prostate-Specific Antigen","Mice","Androgen Receptor Antagonists"],"keywords":["LNCaP","Androgen receptor","Bicalutamide","Androgen","Endocrinology","Prostate cancer","Internal medicine","Dihydrotestosterone","Cancer research","Biology","Antiandrogen","Medicine","Cancer","Hormone"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T12:43:55.932502Z","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":[]}