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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2011

Autores

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

Revista

Título: PLoS ONE

Vol. 6 Nº 8

ISSN: 1932-6203

Editora: Public Library of Science

Indexação

ISI Web of Knowledge - 35 Citações

Scopus - 39 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 11