Expression of Novel Molecules, MICAL2-PV (MICAL2 Prostate Cancer Variants), Increases with High Gleason Score and Prostate Cancer Progression

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Abstract
Purpose: The aim of this study is to identify novel molecular targets for development of novel treatment or diagnostic markers of prostate cancer through genome-wide cDNA microarray analysis of prostate cancer cells purified by laser microdissection. Experimental Design and Results: Here, we identified molecule interacting with CasL-2 prostate cancer variants (MICAL2-PV), novel splicing variants of MICAL2, showing overexpression in prostate cancer cells. Immunohistochemical analysis using an antibody generated specific to MICAL2-PV revealed that MICAL2-PV was expressed in the cytoplasm of cancer cells with various staining patterns and intensities, whereas it was not or hardly detectable in adjacent normal prostate epithelium or prostatic intraepithelial neoplasia. Interestingly, immunohistochemical analysis of 105 prostate cancer specimens on the tissue microarray indicated that MICAL2-PV expression status was strongly correlated with Gleason scores (P < 0.0001) or tumor classification (P < 0.0001). Furthermore, the expression levels of MICAL2-PVs were also concordant to those of c-Met, a marker of tumor progression, with statistical significance (P = 0.0018). To investigate its potential of molecular therapeutic target for prostate cancers, we knocked down endogenous MICAL2-PVs in prostate cancer cells by small interfering RNA, which resulted in the significant reduction of prostate cancer cell viability. Conclusions: Our findings suggest that MICAL2-PV is likely to be involved in cancer progression of prostate cancer and could be a candidate as a novel molecular marker and/or target for treatment of prostate cancers with high Gleason score.