{"doi":"10.3390/cancers12123640","title":"Growth Hormone Upregulates Mediators of Melanoma Drug Efflux and Epithelial-to-Mesenchymal Transition In Vitro and In Vivo","abstract":"Growth hormone (GH) and the GH receptor (GHR) are expressed in a wide range of malignant tumors including melanoma. However, the effect of GH/insulin-like growth factor (IGF) on melanoma in vivo has not yet been elucidated. Here we assessed the physical and molecular effects of GH on mouse melanoma B16-F10 and human melanoma SK-MEL-30 cells in vitro. We then corroborated these observations with syngeneic B16-F10 tumors in two mouse lines with different levels of GH/IGF: bovine GH transgenic mice (bGH; high GH, high IGF-1) and GHR gene-disrupted or knockout mice (GHRKO; high GH, low IGF-1). In vitro, GH treatment enhanced mouse and human melanoma cell growth, drug retention and cell invasion. While the in vivo tumor size was unaffected in both bGH and GHRKO mouse lines, multiple drug-efflux pumps were up regulated. This intrinsic capacity of therapy resistance appears to be GH dependent. Additionally, epithelial-to-mesenchymal transition (EMT) gene transcription markers were significantly upregulated in vivo supporting our current and recent in vitro observations. These syngeneic mouse melanoma models of differential GH/IGF action can be valuable tools in screening for therapeutic options where lowering GH/IGF-1 action is important.","journal":"Cancers","year":2020,"id":99571,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.945,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":445186,"name":"Reetobrata Basu","orcid":"0000-0001-8415-1356","position":1,"is_corresponding":false},{"id":491140,"name":"Samuel Mathes","orcid":null,"position":2,"is_corresponding":false},{"id":264505,"name":"Nathan Arnett","orcid":"0000-0002-7355-4691","position":3,"is_corresponding":false},{"id":445188,"name":"Silvana Duran‐Ortiz","orcid":"0000-0001-8870-4077","position":4,"is_corresponding":false},{"id":446275,"name":"Kevin Funk","orcid":null,"position":5,"is_corresponding":false},{"id":490072,"name":"Alison Brittain","orcid":"0000-0001-8505-6465","position":6,"is_corresponding":false},{"id":445187,"name":"Prateek Kulkarni","orcid":"0000-0002-4557-6535","position":7,"is_corresponding":false},{"id":491141,"name":"Joseph Terry","orcid":null,"position":8,"is_corresponding":false},{"id":31846,"name":"Emily F. Davis-Marcisak","orcid":"0000-0001-8624-1013","position":9,"is_corresponding":false},{"id":491142,"name":"Jordyn T. Singerman","orcid":null,"position":10,"is_corresponding":false},{"id":491143,"name":"Brooke E. Henry","orcid":null,"position":11,"is_corresponding":false},{"id":353849,"name":"Edward O. List","orcid":"0000-0002-8230-6331","position":12,"is_corresponding":false},{"id":445185,"name":"Darlene E. Berryman","orcid":"0000-0003-4240-9229","position":13,"is_corresponding":false},{"id":291366,"name":"John J. Kopchick","orcid":"0000-0003-4561-2177","position":14,"is_corresponding":false},{"id":445189,"name":"Yanrong Qian","orcid":"0000-0002-3950-2759","position":0,"is_corresponding":true}],"reference_count":131,"raw_metadata":null,"created_at":"2026-07-18T22:38:09.754371Z","pmid":"33291663","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":[]}