Expression of novel molecules, MICAL2-PV (MICAL2 prostate cancer variants), increases with high Gleason score and prostate cancer progression
Expression of novel molecules, MICAL2-PV (MICAL2 prostate cancer variants), increases with high Gleason score and prostate cancer progression
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DOI：
10.1158/1078-0432.ccr-05-1995
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发表时间：
2006-05-01
影响因子：
11.5
通讯作者：
Nakagawa, H
中科院分区：
文献类型：
--
作者：
Ashida, S;Furihata, M;Nakagawa, H
目的：本研究的目的是通过激光显微切割纯化的前列腺癌细胞的全基因组cDNA微阵列分析，确定新的分子靶点，用于开发新的治疗或诊断前列腺癌的标志物。实验设计和结果：在这里，我们确定了与CasL-2前列腺癌变体（MICAL 2-PV）相互作用的分子，MICAL 2的新剪接变体，在前列腺癌细胞中显示过表达。使用产生的MICAL 2-PV特异性抗体的免疫组织化学分析显示，MICAL 2-PV在癌细胞的细胞质中以各种染色模式和强度表达，而在相邻的正常前列腺上皮或前列腺上皮内瘤变中不能或几乎不能检测到。有趣的是，对组织芯片上的105个前列腺癌标本的免疫组织化学分析表明MICAL 2-PV表达状态与Gleason评分（P < 0.0001）或肿瘤分类（P < 0.0001）强烈相关。此外，MICAL 2-PV的表达水平也与肿瘤进展标志物c-Met的表达水平一致，具有统计学意义（P = 0.0018）。为了研究其作为前列腺癌分子治疗靶点的潜力，我们用小干扰RNA（small interfering RNA，siRNA）敲低了前列腺癌细胞中的内源性MICAL 2-PVs，导致前列腺癌细胞活力显著降低。我们的研究结果表明，MICAL 2-PV可能参与前列腺癌的进展，并可能成为一种新的候选分子标记物和/或肿瘤标志物。或用于治疗具有高Gleason评分的前列腺癌的靶点。
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.