Cooperation of Loss of and Inflammation in Prostate Cancer Initiation

Overview

Journal Dis Model Mech

Specialty General Medicine

Date 2018 Sep 30

PMID 30266798

Citations 24

Authors

Clementine Le Magnen

Renu K Virk

Aditya Dutta

Jaime Yeji Kim

Sukanya Panja

Zoila A Lopez-Bujanda

Andrea Califano

Charles G Drake

Antonina Mitrofanova

Cory Abate-Shen

Affiliations

Soon will be listed here.

Abstract

Although it is known that inflammation plays a critical role in prostate tumorigenesis, the underlying processes are not well understood. Based on analysis of genetically engineered mouse models combined with correlative analysis of expression profiling data from human prostate tumors, we demonstrate a reciprocal relationship between inflammation and the status of the homeobox gene associated with prostate cancer initiation. We find that cancer initiation in aged mutant mice correlates with enrichment of specific immune populations and increased expression of immunoregulatory genes. Furthermore, expression of these immunoregulatory genes is similarly increased in human prostate tumors having low levels of expression. We further show that induction of prostatitis in mutant mice accelerates prostate cancer initiation, which is coincident with aberrant cellular plasticity and differentiation. Correspondingly, human prostate tumors having low levels of have de-regulated expression of genes associated with these cellular processes. We propose that loss of function of accelerates inflammation-driven prostate cancer initiation potentially via aberrant cellular plasticity and impairment of cellular differentiation.This article has an associated First Person interview with the first author of the paper.

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