Cysteine-rich secretory protein-3 (CRISP3) is strongly up-regulated in prostate carcinomas with the TMPRSS2-ERG fusion gene

• Published in: PloS one 2011-07, Vol.6 (7), p.e22317-e22317
• Main Authors: Ribeiro, Franclim R, Paulo, Paula, Costa, Vera L, Barros-Silva, João D, Ramalho-Carvalho, João, Jerónimo, Carmen, Henrique, Rui, Lind, Guro E, Skotheim, Rolf I, Lothe, Ragnhild A, Teixeira, Manuel R
• Format: Article
• Language: English
• Subjects: Aberration; Aged; Analysis; Biology; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biopsy; Blotting, Western; Cancer genetics; Case-Control Studies; Cell adhesion; Cellular signal transduction; Chromatin; Chromatin Immunoprecipitation; Cysteine; Cystine; Deregulation; Disease prevention; Enzymes; Epigenetics; ERG gene; Fusion protein; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; Genetics; Genome, Human; Genomes; Genomics; Humans; Immunoenzyme Techniques; Immunohistochemistry; Immunology; Immunoprecipitation; In Situ Hybridization, Fluorescence; Male; Medical prognosis; Medical research; Medicine; Membrane proteins; Middle Aged; Oligonucleotide Array Sequence Analysis; Oncogene Proteins, Fusion - genetics; Oncogene Proteins, Fusion - metabolism; Oncology; Overexpression; Pathology; Pathways; Prostate - metabolism; Prostate - pathology; Prostate cancer; Prostate carcinoma; Prostatic Hyperplasia - genetics; Prostatic Hyperplasia - metabolism; Prostatic Hyperplasia - pathology; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger - genetics; Salivary Proteins and Peptides - genetics; Salivary Proteins and Peptides - metabolism; Seminal Plasma Proteins - genetics; Seminal Plasma Proteins - metabolism; Thiols; Transcription (Genetics); Transcription factors; Transduction; Up-Regulation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0022317

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