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Title: Transgenic Expression Of Mitochondrial Chaperone Trap1 Accelerates Prostate Cancer Development      
ID:
PRJNA321266
description:
Protein homeostasis, or proteostasis is critical for organelle function, including mitochondria, but its role in cancer is controversial. Here, we show that transgenic mice expressing the mitochondrial chaperone, TRAP1 in the prostate develop prostatic hyperplasia and cellular atypia. When examined on a Pten+/- background, a common alteration in prostate cancer patients, TRAP1 transgenic mice showed accelerated incidence of invasive prostatic adenocarcinoma, characterized by increased cell proliferation and reduced apoptosis, in situ. Conversely, homozygous deletion of TRAP1 delays prostatic tumorigenesis in Pten+/- mice, without affecting hyperplasia or prostatic intraepithelial neoplasia (PIN). Global RNA sequencing and reverse phase protein array profiling of Pten+/--TRAP1 transgenic tumors reveals modulation of oncogenic networks of cell proliferation, apoptosis, cell motility, DNA damage and metabolism. Mechanistically, reconstitution of Pten+/- prostatic epithelial cells with TRAP1 results in increased cell proliferation, reduced apoptosis, heightened cell invasion, and no changes in mitochondrial bioenergetics. Therefore, TRAP1 promotes invasive prostate cancer, and provides an “actionable” therapeutic target in patients with advanced disease. Overall design: RNA-seq for Pten +/- mice with and without transgenic Trap1
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA321266
authentication:
none
authorization:
none
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject