Upregulation and overexpression of DVL1, the human counterpart of the Drosophila dishevelled gene, in prostate cancer.
OBJECTIVE
The Wnt/beta-catenin signaling pathway is one of the main carcinogenic mechanisms in human malignancies including prostate cancer. Recently, the DVL1 gene was identified as a middle molecule of the Wnt/beta-catenin signaling pathway. In addition, alterations of the DVL1 gene have been reported in breast and cervical cancer. The abnormality of beta-catenin in prostate cancer has been well studied, so the examination of the DVL1 gene in prostate cancer is appealing.


METHODS
We investigated DVL1 messenger RNA alterations by semiquantitative PCR (SQ-PCR) in 20 primary prostate cancers and assessed the protein expression by immunohistochemical analysis in the same samples. In addition, DVL1 and beta-catenin protein expression was evaluated with a new validated set of 20 prostate cancers.


RESULTS
SQ-PCR revealed significant overexpression of DVL1 in prostate cancer (65%). Upregulation of the DVL1 gene product in prostate cancer was confirmed by immunostaining. With SQ-PCR and immunostaining, none of the cases showed underexpression or downregulation of DVL1. In addition, the data showed correlations between DVL1 mRNA and protein expression. Interestingly, the expression level of DVL1 increased with worsening histological grade. In addition, a correlation between DVL1 expression and beta-catenin expression was confirmed.


CONCLUSIONS
DVL1 was overexpressed in prostate cancer and its overexpression might be related to prostate cancer progression through the Wnt/beta-catenin pathway.
Mizutani
Kazunori
K
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan.
Miyamoto
Shizuyo
S
Nagahata
Takemitsu
T
Konishi
Noboru
N
Emi
Mitsuru
M
Onda
Masamitsu
M
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000032:analysis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D051176:beta Catenin / Q000032:analysis*
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C000606578:DVL1 protein, human; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D051176:beta Catenin; C000606588:dsh protein, Drosophila