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An androgen receptor regulated gene score is associated with epithelial to mesenchymal transition features in triple negative breast cancers

Rajarajan, S and Snijesh, VP and Anupama, CE and Nair, MG and Mavatkar, AD and Naidu, CM and Patil, S and Nimbalkar, VP and Alexander, A and Pillai, M and Jolly, MK and Sabarinathan, R and Ramesh, RS and BS, S and Prabhu, JS (2023) An androgen receptor regulated gene score is associated with epithelial to mesenchymal transition features in triple negative breast cancers. In: Translational Oncology, 37 .

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Official URL: https://doi.org/10.1016/j.tranon.2023.101761


Background: Androgen receptor (AR) is considered a marker of better prognosis in hormone receptor positive breast cancers (BC), however, its role in triple negative breast cancer (TNBC) is controversial. This may be attributed to intrinsic molecular differences or scoring methods for AR positivity. We derived AR regulated gene score and examined its utility in BC subtypes. Methods: AR regulated genes were derived by applying a bioinformatic pipeline on publicly available microarray data sets of AR+ BC cell lines and gene score was calculated as average expression of six AR regulated genes. Tumors were divided into AR high and low based on gene score and associations with clinical parameters, circulating androgens, survival and epithelial to mesenchymal transition (EMT) markers were examined, further evaluated in invitro models and public datasets. Results: 53 (133/249) tumors were classified as AR gene score high and were associated with significantly better clinical parameters, disease-free survival (86.13 vs 72.69 months, log rank p = 0.032) when compared to AR low tumors. 36 of TNBC (N = 66) were AR gene score high with higher expression of EMT markers (p = 0.024) and had high intratumoral levels of 5α-reductase, enzyme involved in intracrine androgen metabolism. In MDA-MB-453 treated with dihydrotestosterone, SLUG expression increased, E-cadherin decreased with increase in migration and these changes were reversed with bicalutamide. Similar results were obtained in public datasets. Conclusion: Deciphering the role of AR in BC is difficult based on AR protein levels alone. Our results support the context dependent function of AR in driving better prognosis in ER positive tumors and EMT features in TNBC tumors. © 2023

Item Type: Journal Article
Publication: Translational Oncology
Publisher: Neoplasia Press, Inc.
Additional Information: The copyright for this article belongs to the Authors.
Keywords: androgen receptor; androstanolone; bicalutamide; epidermal growth factor receptor 2; estrogen receptor; Ki 67 antigen; progesterone receptor; testosterone; transcription factor Slug; transcription factor ZEB1; uvomorulin, adult; androgen metabolism; Article; bioinformatics; breast cancer cell line; cancer survival; cell migration; cell proliferation; chemoluminescence; controlled study; diagnostic test accuracy study; differential expression analysis; disease free survival; down regulation; epithelial mesenchymal transition; female; follow up; gene expression; gene ontology; gene overexpression; human; human cell; human tissue; immunofluorescence; immunohistochemistry; in vitro study; longitudinal study; major clinical study; MDA-MB-435 cell line; MDA-MB-453 cell line; MTT assay; observational study; overall survival; protein expression; quality control; real time polymerase chain reaction; receiver operating characteristic; RNA extraction; tissue microarray; triple negative breast cancer; upregulation; Western blotting
Department/Centre: Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited: 08 Nov 2023 04:47
Last Modified: 08 Nov 2023 04:47
URI: https://eprints.iisc.ac.in/id/eprint/83022

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