Expression of the ELAV-like protein HuR in human prostate carcinoma is an indicator of disease relapse and linked to COX-2 expression.
The human ELAV-like protein HuR is involved in the stabilization of the mRNAs of a group of genes implicated in the regulation of cellular growth, angiogenesis and rapid inflammatory response. HuR is a nuclear shuttling protein, translocating bound mRNAs from the nucleus to the cytoplasm. We have previously observed an increased expression of cyclooxygenase-2 (COX-2) in prostate cancer while cell culture studies have shown that HuR stabilizes the mRNA of COX-2. Based on these mechanistic data, we aimed to investigate the role of HuR in prostate cancer by a tissue-based analysis combined with functional evaluation using a cell culture approach. Investigating 104 primary prostate carcinomas by immunohistochemistry, we found HuR expression to be shifted from a nuclear staining in normal prostate glands to a cytoplasmic staining in carcinoma tissue (p<0.0001). Cytoplasmic HuR expression was significantly correlated with COX-2 expression (p=0.005). Loss of nuclear HuR expression was an indicator of earlier PSA-relapse both in univariate (p=0.04) and multivariate survival analysis (p=0.04). HuR inhibition by Leptomycin B reduced the inducibility of COX-2 in PC-3 prostate cancer cells. We found that the subcellular localization of HuR is deregulated in a subset of prostate carcinomas, and that this deregulation is linked to an altered expression of the tumorigenic COX-2 protein as well as to an adverse patient prognosis. Our results point to a potential prognostic role of HuR expression in prostate cancer diagnostics and propose HuR as a future therapeutic target in prostate cancer therapy.
Niesporek
Silvia
S
Institute of Pathology, Charité Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, Berlin, Germany. silvia.niesporek@charite.de
Kristiansen
Glen
G
Thoma
Andrea
A
Weichert
Wilko
W
Noske
Aurelia
A
Buckendahl
Ann-Christin
AC
Jung
Klaus
K
Stephan
Carsten
C
Dietel
Manfred
M
Denkert
Carsten
C
D000368:Aged; D000954:Antigens, Surface / Q000096:biosynthesis*; D002277:Carcinoma / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D018450:Disease Progression; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011471:Prostatic Neoplasms / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D012008:Recurrence; D016896:Treatment Outcome
D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D005231:Fatty Acids, Unsaturated; D016601:RNA-Binding Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C038753:leptomycin B