{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:44:41Z","timestamp":1791902681294,"version":"4.3.4"},"reference-count":164,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"John J. Kopchick Molecular and Cellular Biology \/ Translational Biomedical Sciences Research Fellowship award (Ohio University, Athens, OH, USA E.D.)"},{"name":"State of Ohio\u2019s Eminent Scholar Program to J.J.K., which includes a gift from Milton and Lawrence Goll, the American Veterans, the Institute For Molecular Medicine and Aging (Ohio University, Athens, OH, USA)"},{"name":"Molecular and Cellular Biology Program (Ohio University, Athens, OH, USA)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Growth hormone (GH) signaling has been implicated in tumor progression and therapy resistance across multiple cancer types, yet its role in bladder cancer remains largely unexplored. In this study, we investigated the impact of GH and its receptor (GHR) on therapy resistance and disease progression in urothelial carcinoma (UC) through integrated transcriptomic and in vitro analyses. Transcriptomic profiling of The Cancer Genome Atlas bladder cancer cohort revealed that high tumoral GHR expression was associated with differential upregulation of genes involved in drug efflux, epithelial-to-mesenchymal transition (EMT), and extracellular matrix (ECM) remodeling. Notably, elevated GHR levels correlated with significantly reduced overall survival in patients with UC. In parallel, in vitro experiments demonstrated that GH promotes chemoresistance in UC cell lines via upregulation of ATP-binding cassette-containing (ABC) transporters and activation of EMT. GH also modulated ECM-remodeling-associated genes in a chemotherapy-dependent manner, including matrix metalloproteinases and tissue inhibitors of metalloproteinases. Importantly, these effects were abrogated by Pegvisomant, a GHR antagonist, indicating the functional relevance of GH\/GHR signaling in the mediation of these phenotypes. Collectively, our findings support a mechanistic role for GH signaling in driving therapy resistance and tumor aggressiveness in bladder cancer and suggest GHR antagonism as a potential therapeutic strategy to improve treatment outcomes.<\/jats:p>","DOI":"10.3390\/ijms26157113","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T16:04:51Z","timestamp":1753286691000},"page":"7113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Growth Hormone Signaling in Bladder Cancer: Transcriptomic Profiling of Patient Samples and In Vitro Evidence of Therapy Resistance via ABC Transporters and EMT Activation"],"prefix":"10.3390","volume":"26","author":[{"given":"Emily","family":"Davis","sequence":"first","affiliation":[{"name":"Institute for Molecular Medicine and Aging, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA"},{"name":"Molecular and Cellular Biology Program, College of Arts and Sciences, Ohio University, Athens, OH 45701, USA"},{"name":"Department of Biological Sciences, College of Arts and Sciences, Ohio University, Athens, OH 45701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia J.","family":"Caggiano","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine and Aging, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA"},{"name":"Honors Tutorial College, Ohio University, Athens, OH 45701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Munholland","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine and Aging, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA"},{"name":"Department of Biological Sciences, College of Arts and Sciences, Ohio University, Athens, OH 45701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8415-1356","authenticated-orcid":false,"given":"Reetobrata","family":"Basu","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine and Aging, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA"},{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4240-9229","authenticated-orcid":false,"given":"Darlene E.","family":"Berryman","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine and Aging, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA"},{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Kopchick","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine and Aging, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA"},{"name":"Molecular and Cellular Biology Program, College of Arts and Sciences, Ohio University, Athens, OH 45701, USA"},{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"ref_1","unstructured":"Brinkman, J.E., Tariq, M.A., Leavitt, L., and Sharma, S. 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