Cysteine-Rich Secretory Protein-3 (CRISP3) Is Strongly Up-Regulated in Prostate Carcinomas with the TMPRSS2-ERG Fusion Gene

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Ribeiro, FR (Author) Other; Paulo, P (Author) Other; Costa, VL (Author) Other; Barros Silva, JD (Author) Other; Ramalho Carvalho, J (Author) Other; Carmen Jeronimo (Author) ICBAS; henrique, rmf (Author) ICBAS; Lind, GE (Author) Other; Skotheim, RI (Author) Other; Lothe, RA (Author) Other; Manuel R Teixeira (Author) ICBAS

Journal

Title: PLoS ONE

Vol. 6 No. 8

ISSN: 1932-6203

Publisher: Public Library of Science

Indexing

ISI Web of Knowledge - 35 Citations

Scopus - 39 Citations

Other information

Authenticus ID: P-002-PMD

DOI: 10.1371/journal.pone.0022317

Abstract (EN): A large percentage of prostate cancers harbor TMPRSS2-ERG gene fusions, leading to aberrant overexpression of the transcription factor ERG. The target genes deregulated by this rearrangement, however, remain mostly unknown. To address this subject we performed genome-wide mRNA expression analysis on 6 non-malignant prostate samples and 24 prostate carcinomas with (n = 16) and without (n = 8) TMPRSS2-ERG fusion as determined by FISH. The top-most differentially expressed genes and their associations with ERG over-expression were technically validated by quantitative real-time PCR and biologically validated in an independent series of 200 prostate carcinomas. Several genes encoding metabolic enzymes or extracellular/transmembrane proteins involved in cell adhesion, matrix remodeling and signal transduction pathways were found to be co-expressed with ERG. Within those significantly over-expressed in fusion-positive carcinomas, CRISP3 showed more than a 50-fold increase when compared to fusion-negative carcinomas, whose expression levels were in turn similar to that of non-malignant ;samples. In the independent validation series, ERG and CRISP3 mRNA levels were strongly correlated (r(s) = 0.65, p < 0.001) and both were associated with pT3 disease staging. Furthermore, immunohistochemistry results showed CRISP3 protein overexpression in 63% of the carcinomas and chromatin immunoprecipitation with an anti-ERG antibody showed that CRISP3 is a direct target of the transcription factor ERG. We conclude that ERG rearrangement is associated with significant expression alterations in genes involved in critical cellular pathways that define a subset of locally advanced PCa. In particular, we show that CRISP3 is a direct target of ERG that is strongly overexpressed in PCa with the TMPRSS2-ERG fusion gene.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11