Cysteine-rich secretory protein-3 (CRISP3) is strongly up-regulated in prostate carcinomas with the TMPRSS2-ERG fusion gene.
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...
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2011
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oai:doaj.org-article:35096269b807436484e8aab535a5939d2021-11-18T06:49:41ZCysteine-rich secretory protein-3 (CRISP3) is strongly up-regulated in prostate carcinomas with the TMPRSS2-ERG fusion gene.1932-620310.1371/journal.pone.0022317https://doaj.org/article/35096269b807436484e8aab535a5939d2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21814574/?tool=EBIhttps://doaj.org/toc/1932-6203A 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.Franclim R RibeiroPaula PauloVera L CostaJoão D Barros-SilvaJoão Ramalho-CarvalhoCarmen JerónimoRui HenriqueGuro E LindRolf I SkotheimRagnhild A LotheManuel R TeixeiraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e22317 (2011) |
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DOAJ |
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Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Franclim R Ribeiro Paula Paulo Vera L Costa João D Barros-Silva João Ramalho-Carvalho Carmen Jerónimo Rui Henrique Guro E Lind Rolf I Skotheim Ragnhild A Lothe Manuel R Teixeira Cysteine-rich secretory protein-3 (CRISP3) is strongly up-regulated in prostate carcinomas with the TMPRSS2-ERG fusion gene. |
| description |
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. |
| format |
article |
| author |
Franclim R Ribeiro Paula Paulo Vera L Costa João D Barros-Silva João Ramalho-Carvalho Carmen Jerónimo Rui Henrique Guro E Lind Rolf I Skotheim Ragnhild A Lothe Manuel R Teixeira |
| author_facet |
Franclim R Ribeiro Paula Paulo Vera L Costa João D Barros-Silva João Ramalho-Carvalho Carmen Jerónimo Rui Henrique Guro E Lind Rolf I Skotheim Ragnhild A Lothe Manuel R Teixeira |
| author_sort |
Franclim R Ribeiro |
| title |
Cysteine-rich secretory protein-3 (CRISP3) is strongly up-regulated in prostate carcinomas with the TMPRSS2-ERG fusion gene. |
| title_short |
Cysteine-rich secretory protein-3 (CRISP3) is strongly up-regulated in prostate carcinomas with the TMPRSS2-ERG fusion gene. |
| title_full |
Cysteine-rich secretory protein-3 (CRISP3) is strongly up-regulated in prostate carcinomas with the TMPRSS2-ERG fusion gene. |
| title_fullStr |
Cysteine-rich secretory protein-3 (CRISP3) is strongly up-regulated in prostate carcinomas with the TMPRSS2-ERG fusion gene. |
| title_full_unstemmed |
Cysteine-rich secretory protein-3 (CRISP3) is strongly up-regulated in prostate carcinomas with the TMPRSS2-ERG fusion gene. |
| title_sort |
cysteine-rich secretory protein-3 (crisp3) is strongly up-regulated in prostate carcinomas with the tmprss2-erg fusion gene. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/35096269b807436484e8aab535a5939d |
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