creators_name: Kalra, Rashi
creators_name: Bhagyaraj, Ella
creators_name: Tiwari, Drishti
creators_name: Nanduri, Ravikanth
creators_name: Chacko, Anuja P
creators_name: Jain, Monika
creators_name: Mahajan, Sahil
creators_name: Khatri, Neeraj
creators_name: Gupta, Pawan
type: article
datestamp: 2019-03-20 09:49:35
lastmod: 2019-03-20 09:49:35
metadata_visibility: show
title: AIRE promotes androgen-independent prostate cancer by directly regulating IL-6 and modulating tumor microenvironment.
ispublished: pub
subjects: QR
note: Open Access
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.
date: 2018-05-25
date_type: published
publication: Oncogenesis
volume: 7
number: 5
publisher: Springer Nature
pagerange: 1-15
refereed: TRUE
issn: 2157-9024
official_url: https://www.nature.com/articles/s41389-018-0053-7
citation:   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