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

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title AIRE promotes androgen-independent prostate cancer by directly regulating IL-6 and modulating tumor microenvironment.
 
Creator Kalra, Rashi
Bhagyaraj, Ella
Tiwari, Drishti
Nanduri, Ravikanth
Chacko, Anuja P
Jain, Monika
Mahajan, Sahil
Khatri, Neeraj
Gupta, Pawan
 
Subject QR Microbiology
 
Description 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.
 
Publisher Springer Nature
 
Date 2018-05-25
 
Type Article
PeerReviewed
 
Relation https://www.nature.com/articles/s41389-018-0053-7
http://crdd.osdd.net/open/2184/
 
Identifier 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