Faculty Collaboration Database

ETS Related Gene mediated Androgen Receptor Aggregation and Endoplasmic Reticulum Stress in Prostate Cancer Development. Sci Rep 2017 Apr 24;7(1):1109

Date

04/26/2017

Pubmed ID

28439080

Pubmed Central ID

PMC5430720

DOI

10.1038/s41598-017-01187-4

Scopus ID

2-s2.0-85018452489 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

Mechanistic studies of deregulated ERG in prostate cancer and other cancers continue to enhance its role in cancer biology and its utility as a biomarker and therapeutic target. Here, we show that ERG, through its physical interaction with androgen receptor, induces AR aggregation and endoplasmic reticulum stress in the prostate glands of ERG transgenic mice. Histomorphological alterations and the expression of ER stress sensors Atf6, Ire1α, Perk, their downstream effectors Grp78/BiP and eIF2α in ERG transgenic mouse prostate glands indicate the presence of chronic ER stress. Transient activation of apoptotic cell death during early age correlated well with the differential regulation of ER stress sensors, in particular Perk. Epithelial cells derived from ERG transgenic mouse prostates have increased prostasphere formation with resistance to radiation induced cell death. Continued activation of cell survival factors, Atf6 and Ire1α during chronic ER stress due to presence of ERG in prostate epithelium induces survival pathways and provides a selection pressure in the continuum of ERG dependent neoplastic process. These novel insights will enhance the understanding of the mechanistic functions of ERG in prostate tumor biology and towards development of early targeted therapeutic strategies for prostate cancer.

Author List

Sreenath TL, Macalindong SS, Mikhalkevich N, Sharad S, Mohamed A, Young D, Borbiev T, Xavier C, Gupta R, Jamal M, Babcock K, Tan SH, Nevalainen MT, Dobi A, Petrovics G, Sesterhenn IA, Rosner IL, Bieberich CJ, Nelson P, Vasioukhin V, Srivastava S

MESH terms used to index this publication - Major topics in bold

Animals
Endoplasmic Reticulum Stress
Gene Expression Profiling
Histocytochemistry
Immunohistochemistry
Male
Mice, Transgenic
Microscopy
Prostate
Prostatic Neoplasms
Protein Aggregation, Pathological
Receptors, Androgen
Transcriptional Regulator ERG