{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:08:28Z","timestamp":1791922108414,"version":"4.3.4"},"reference-count":53,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz","doi-asserted-by":"publisher","award":["503\/0\u2013078\u201304\/503\u201301\u2013001"],"award-info":[{"award-number":["503\/0\u2013078\u201304\/503\u201301\u2013001"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]},{"award":["503\/0\u2013078\u201304\/503\u201301\u2013001"],"award-info":[{"award-number":["503\/0\u2013078\u201304\/503\u201301\u2013001"]}],"id":[{"id":"https:\/\/ror.org\/02t4ekc95","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Glucocorticoids, including dexamethasone (DEX), are known to demonstrate anti-inflammatory activity, suppress steroidogenesis, and mitigate the adverse effects of chemotherapy. They are therefore widely employed for managing solid malignancies. Emerging evidence indicates that DEX modulates both systemic and local renin\u2013angiotensin system (RAS) activity, including genomic signaling via the glucocorticoid receptor (GR). Methods: DEX-dependent transcriptional responses for the angiotensin receptor genes (AGTR1, AGTR2, MAS1, and LNPEP) were evaluated in ovarian (SKOV3, KURAMOCHI) and prostate (DU-145, PC3) cancer cell lines. The cells were cultured under different serum conditions to determine the influence of nutrient availability on tumor progression. Results: DEX demonstrated distinct mechanisms of action between the ovarian and prostate cancer models. It was found to promote cancer cell survival through tissue-specific modulation of metabolic activity, clonogenic capacity, cell cycle distribution, and apoptotic responses. These effects were accompanied by condition-dependent alterations in angiotensin receptor gene expression. Hence, DEX may mediate the remodeling of local RAS signaling, which may be significant in overall survival and disease-free survival. The findings also indicate a previously-unreported NR3C1\u2013LNPEP correlation, which was consistently observed across in vitro systems and patient datasets, in both ovarian- and prostate-derived cancer models. Conclusions: DEX appears to exert context-dependent regulation of RAS-associated gene networks in ovarian and prostate cancer, suggesting a role in tumor adaptive responses and potentially in therapeutic contexts.<\/jats:p>","DOI":"10.3390\/cancers18121998","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T09:18:43Z","timestamp":1781860723000},"page":"1998","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dexamethasone as a Modulator of Renin\u2013Angiotensin System Receptor Expression in Prostate and Ovarian Cancer Cells Under Standard and Low-Serum Conditions"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6228-9416","authenticated-orcid":false,"given":"Weronika","family":"Broszkiewicz","sequence":"first","affiliation":[{"name":"Department of Comparative Endocrinology, Medical University of Lodz, Zeligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5901-9821","authenticated-orcid":false,"given":"Natasza","family":"Wiertek-P\u0142oszaj","sequence":"additional","affiliation":[{"name":"Department of Comparative Endocrinology, Medical University of Lodz, Zeligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Gajewska","sequence":"additional","affiliation":[{"name":"Department of Comparative Endocrinology, Medical University of Lodz, Zeligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Wosiak","sequence":"additional","affiliation":[{"name":"Department of Comparative Endocrinology, Medical University of Lodz, Zeligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7501-8369","authenticated-orcid":false,"given":"Kamila","family":"Domi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Comparative Endocrinology, Medical University of Lodz, Zeligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1210\/edrv-5-1-25","article-title":"Physiological Functions of Glucocorticoids in Stress and Their Relation to Pharmacological Actions","volume":"5","author":"Munck","year":"1984","journal-title":"Endocr. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1159\/000530701","article-title":"Glucocorticoids and Water Balance: Implications for Hyponatremia Management and Pituitary Surgery","volume":"113","author":"Goldschlager","year":"2023","journal-title":"Neuroendocrinology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1161\/HYPERTENSIONAHA.107.091603","article-title":"Developmental Programming of Renal Glucocorticoid Sensitivity and the Renin-Angiotensin System","volume":"50","author":"Wyrwoll","year":"2007","journal-title":"Hypertension"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000227803","article-title":"Excess of Glucocorticoid Induces Cardiac Dysfunction via Activating Angiotensin II Pathway","volume":"24","author":"Roy","year":"2009","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1007\/s12020-014-0196-z","article-title":"Glucocorticoids activate the local renin\u2013angiotensin system in bone: Possible mechanism for glucocorticoid-induced osteoporosis","volume":"47","author":"Yongtao","year":"2014","journal-title":"Endocrine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1210\/en.2015-1197","article-title":"Maternal Dexamethasone Treatment Alters Tissue and Circulating Components of the Renin-Angiotensin System in the Pregnant Ewe and Fetus","volume":"156","author":"Forhead","year":"2015","journal-title":"Endocrinology"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Shahbaz, S., Oyegbami, O., Saito, S., Osman, M., Sligl, W., and Elahi, S. (2022). Differential effects of age, sex and dexamethasone therapy on ACE2\/TMPRSS2 expression and susceptibility to SARS-CoV-2 infection. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1021928"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0960-0760(93)90119-H","article-title":"Angiotensin II and dexamethasone regulate angiotensinogen mRNA by different mechanisms","volume":"45","author":"Hackenthal","year":"1993","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"102077","DOI":"10.1016\/j.jgo.2024.102077","article-title":"Corticosteroid therapy in older adults with cancer: Expert recommendations from a task force of the International Society of Geriatric Oncology","volume":"16","author":"Bartsch","year":"2025","journal-title":"J. Geriatr. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Khadka, S., Druffner, S.R., Duncan, B.C., and Busada, J.T. (2023). Glucocorticoid regulation of cancer development and progression. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1161768"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1158\/1078-0432.CCR-17-0989","article-title":"The Glucocorticoid Receptor Is a Key Player for Prostate Cancer Cell Survival and a Target for Improved Antiandrogen Therapy","volume":"24","author":"Puhr","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.ygyno.2017.04.012","article-title":"High glucocorticoid receptor expression predicts short progression-free survival in ovarian cancer","volume":"146","author":"Veneris","year":"2017","journal-title":"Gynecol. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"12505","DOI":"10.1038\/s41598-020-68668-x","article-title":"Serum deprivation initiates adaptation and survival to oxidative stress in prostate cancer cells","volume":"10","author":"White","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3196","DOI":"10.1158\/1078-0432.CCR-08-2131","article-title":"Administration of Glucocorticoids to Ovarian Cancer Patients Is Associated with Expression of the Anti-apoptotic Genes SGK1 and MKP1\/DUSP1 in Ovarian Tissues","volume":"15","author":"Melhem","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101053","DOI":"10.1016\/j.repbio.2025.101053","article-title":"The impact of dexamethasone on cellular stress responses caused by mild serum deprivation in androgen-insensitive prostate cancer cells","volume":"25","author":"Broszkiewicz","year":"2025","journal-title":"Reprod. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1186\/s12935-023-03080-9","article-title":"The renin-angiotensin-aldosterone system (RAAS) signaling pathways and cancer: Foes versus allies","volume":"23","author":"Hassani","year":"2023","journal-title":"Cancer Cell Int."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Tudrej, P., Kujawa, K.A., Cortez, A.J., and Lisowska, K.M. (2019). Characteristics of in Vivo Model Systems for Ovarian Cancer Studies. Diagnostics, 9.","DOI":"10.3390\/diagnostics9030120"},{"key":"ref_18","unstructured":"(2026, May 18). Human Protein Atlas, Available online: https:\/\/www.proteinatlas.org\/."},{"key":"ref_19","first-page":"72","article-title":"Glucocorticoid Receptor Activity Contributes to Resistance to Androgen-Targeted Therapy in Prostate Cancer","volume":"5","author":"Isikbay","year":"2014","journal-title":"Discov. Oncol."},{"key":"ref_20","first-page":"5887","article-title":"Androgen receptor reverts dexamethasone-induced inhibition of prostate cancer cell proliferation and migration","volume":"17","author":"Guo","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6325","DOI":"10.1158\/1078-0432.CCR-05-0182","article-title":"Glucocorticoids Inhibit Cell Death in Ovarian Cancer and Up-regulate Caspase Inhibitor cIAP2","volume":"11","author":"Runnebaum","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/BF00614309","article-title":"Dose-dependent pharmacokinetics of dexamethasone","volume":"30","author":"Loew","year":"1986","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/bcp.12295","article-title":"Pharmacokinetics of oral vs. intravenous dexamethasone in patients hospitalized with community-acquired pneumonia","volume":"78","author":"Spoorenberg","year":"2014","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.omtm.2020.11.007","article-title":"qPCR and qRT-PCR analysis: Regulatory points to consider when conducting biodistribution and vector shedding studies","volume":"20","author":"Ma","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/s41568-024-00763-x","article-title":"The present and future of the Cancer Dependency Map","volume":"25","author":"Arafeh","year":"2025","journal-title":"Nat. Rev. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"W98","DOI":"10.1093\/nar\/gkx247","article-title":"GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses","volume":"45","author":"Tang","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3861","DOI":"10.1158\/0008-5472.CAN-23-0816","article-title":"Analysis and Visualization of Longitudinal Genomic and Clinical Data from the AACR Project GENIE Biopharma Collaborative in cBioPortal","volume":"83","author":"Kundra","year":"2023","journal-title":"Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"pl1","DOI":"10.1126\/scisignal.2004088","article-title":"Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal","volume":"6","author":"Gao","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_31","unstructured":"Delgado, A., and Guddati, A.K. (2026, May 18). Clinical Endpoints in Oncology-a Primer. Available online: www.ajcr.us\/."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.tiv.2004.03.012","article-title":"Comparison of alamar blue and MTT assays for high through-put screening","volume":"18","author":"Hamid","year":"2004","journal-title":"Toxicol. Vitr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s13048-023-01196-0","article-title":"Tumor metabolism rewiring in epithelial ovarian cancer","volume":"16","author":"Wang","year":"2023","journal-title":"J. Ovarian Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Fontana, F., Anselmi, M., and Limonta, P. (2023). Unraveling the Peculiar Features of Mitochondrial Metabolism and Dynamics in Prostate Cancer. Cancers, 15.","DOI":"10.3390\/cancers15041192"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kokkinopoulou, I., and Moutsatsou, P. (2021). Mitochondrial Glucocorticoid Receptors and Their Actions. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116054"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.4161\/cbt.6.9.4765","article-title":"Cell Cycle Arrest by Glucocorticoids May Protect Normal Tissue and Solid Tumors from Cancer Therapy","volume":"6","author":"Mattern","year":"2007","journal-title":"Cancer Biol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.tcb.2023.05.012","article-title":"The bidirectional relationship between metabolism and cell cycle control","volume":"34","author":"Diehl","year":"2024","journal-title":"Trends Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"11555","DOI":"10.18632\/oncotarget.14135","article-title":"Dexamethasone induces docetaxel and cisplatin resistance partially through up-regulating Kr\u00fcppel-like factor 5 in triple-negative breast cancer","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"ref_39","first-page":"1295","article-title":"Corticosteroids induce chemotherapy resistance in the majority of tumour cells from bone, brain, breast, cervix, melanoma and neuroblastoma","volume":"29","author":"Zhang","year":"2006","journal-title":"Int. J. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"101331","DOI":"10.1016\/j.drup.2025.101331","article-title":"Glucocorticoid receptor activated by dexamethasone promotes the chemoresistance and stemness of lung cancer","volume":"85","author":"Yu","year":"2026","journal-title":"Drug Resist. Updat."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1002\/onco.13960","article-title":"Prospective Study Testing a Simplified Paclitaxel Premedication Regimen in Patients with Early Breast Cancer","volume":"26","author":"Hu","year":"2021","journal-title":"Oncologist"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.ejso.2015.01.034","article-title":"Avoiding perioperative dexamethasone may improve the outcome of patients with rectal cancer","volume":"41","author":"Yu","year":"2015","journal-title":"Eur. J. Surg. Oncol. (EJSO)"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e102770","DOI":"10.1136\/bmjopen-2025-102770","article-title":"Omission of dexamethasone in paclitaxel premedication regimens: Protocol of the multicentre, randomised, non-inferiority DEXASTOP trial","volume":"15","author":"Zietse","year":"2025","journal-title":"BMJ Open"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s13613-025-01567-4","article-title":"Exogenous corticosteroid-induced modulation of RAAS: Potential implications for septic shock biomarker analysis","volume":"15","author":"Uslar","year":"2025","journal-title":"Ann. Intensiv. Care"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Zhan, Z., Lian, Z., and Bai, H. (2024). Dexamethasone inhibited angiotensin II and its receptors to reduce sepsis-induced lung and kidney injury in rats. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0308557"},{"key":"ref_46","first-page":"294","article-title":"The involvement of the renin-angiotensin system (RAS) in cancerogenesis","volume":"54","year":"2008","journal-title":"Postep. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ygyno.2015.08.017","article-title":"Beyond genomics: Critical evaluation of cell line utility for ovarian cancer research","volume":"139","author":"Elias","year":"2015","journal-title":"Gynecol. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1161\/HYPERTENSIONAHA.116.08070","article-title":"Transcriptomic Analysis Reveals Novel Transcription Factors Associated with Renin\u2013Angiotensin\u2013Aldosterone System in Human Atheroma","volume":"68","author":"Nehme","year":"2016","journal-title":"Hypertension"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1091\/mbc.e10-02-0158","article-title":"Insulin-regulated Aminopeptidase Is a Key Regulator of GLUT4 Trafficking by Controlling the Sorting of GLUT4 from Endosomes to Specialized Insulin-regulated Vesicles","volume":"21","author":"Jordens","year":"2010","journal-title":"Mol. Biol. Cell"},{"key":"ref_50","first-page":"369","article-title":"Dominant uptake of fatty acid over glucose by prostate cells: A potential new diagnostic and therapeutic approach","volume":"30","author":"Liu","year":"2010","journal-title":"Anticancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Eidelman, E., Twum-Ampofo, J., Ansari, J., and Siddiqui, M.M. (2017). The Metabolic Phenotype of Prostate Cancer. Front. Oncol., 7.","DOI":"10.3389\/fonc.2017.00131"},{"key":"ref_52","first-page":"551","article-title":"Leucyl and Cystinyl Aminopeptidase as a Prognostic-Related Biomarker in OV Correlating with Immune Infiltrates","volume":"16","author":"Ma","year":"2023","journal-title":"Pharmacogenomics Pers. Med."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Paladini, F., Fiorillo, M.T., Tedeschi, V., Mattorre, B., and Sorrentino, R. (2020). The Multifaceted Nature of Aminopeptidases ERAP1, ERAP2, and LNPEP: From Evolution to Disease. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01576"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/12\/1998\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T09:32:13Z","timestamp":1781861533000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/12\/1998"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,19]]},"references-count":53,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["cancers18121998"],"URL":"https:\/\/doi.org\/10.3390\/cancers18121998","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,19]]}}}