title: AIRE promotes androgen-independent prostate cancer by directly regulating IL-6 and modulating tumor microenvironment.
creator: Kalra, Rashi
creator: Bhagyaraj, Ella
creator: Tiwari, Drishti
creator: Nanduri, Ravikanth
creator: Chacko, Anuja P
creator: Jain, Monika
creator: Mahajan, Sahil
creator: Khatri, Neeraj
creator: 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
type: PeerReviewed
relation: https://www.nature.com/articles/s41389-018-0053-7
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     
relation: http://crdd.osdd.net/open/2184/