AIRE promotes androgen-independent prostate cancer by directly regulating IL-6 and modulating tumor microenvironment.

Kalra, Rashi and Bhagyaraj, Ella and Tiwari, Drishti and Nanduri, Ravikanth and Chacko, Anuja P and Jain, Monika and Mahajan, Sahil and Khatri, Neeraj and Gupta, Pawan (2018) AIRE promotes androgen-independent prostate cancer by directly regulating IL-6 and modulating tumor microenvironment. Oncogenesis, 7 (5). pp. 1-15. ISSN 2157-9024

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Official URL: https://www.nature.com/articles/s41389-018-0053-7

Abstract

Early stage prostate cancers are dependent on androgens for their growth and survival and androgen withdrawal causes them to regress. Progressive prostate cancers eventually acquire androgen independence rendering anti-androgen therapy ineffective. However, the factors leading to this have not been adequately addressed. This study shows that AIRE finds differential expression in androgen-dependent and -independent prostate cancer cells. AIRE expression is more in androgen-independent cells due to its regulation by transcription factor Elk-1. These enhanced levels of AIRE modulate the prostate tumor microenvironment by transcriptionally activating a malignancy gene IL-6 in androgen-independent cells. Additionally, AIRE prevents the cancer cells from anticancer drug-induced death and enhances their invasiveness. Moreover, AIRE by modulating the cytokine milieu skews the tumor-associated macrophage polarization towards M2 phenotype with increased CD206 and CD163 expression. Subcutaneous mouse model of prostate cancer revealed AIRE mice forming a palpable tumor and presents lymphadenopathy however, only a small benign tumor is observed in AIRE mice and lymph nodes appear normal in size. In conclusion, our findings suggest AIRE as a probable factor in promoting prostate cancer progression.

Item Type: Article
Additional Information: Open Access
Subjects: Q Science > QR Microbiology
Depositing User: Dr. K.P.S.Sengar
Date Deposited: 20 Mar 2019 09:49
Last Modified: 20 Mar 2019 09:49
URI: http://crdd.osdd.net/open/id/eprint/2184

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