Diverse functional roles of myosin VI in human prostate cancer Free

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Myosin VI is a unique actin motor that moves to the minus end of the polarized actin filament, a direction opposite to all other characterized myosins. Our previous expression microarray analysis in clinical cancer specimens demonstrated consistent cancer-specific overexpression of myosin VI most prominently in human breast and prostate cancers. In addition, expression levels of myosin VI in a panel of human prostate cancer cell lines positively correlated with the presence of androgen receptor. In light of the diverse biological functions of myosin VI implicated in other model systems, our current study focused on potentially distinctive roles of myosin VI in relation to varying levels of androgen sensitivity in prostate cancer cells. First, through immunohistochemical analysis, we observed well-defined perinuclear staining pattern that is consistently with Golgi localization and suggestive of a secretory function of myosin VI. This Golgi staining pattern is universal and independent of intra-tumor heterogeneity in a subset of cancer specimens but completely absent in other specimens, which demonstrated characteristic diffuse cytoplasmic staining. Next, we conducted immunofluorescent analysis in cell lines with varying levels of androgen receptor. Nearly all the androgen receptor negative PC-3 cells have one or two myosin VI positive foci co-localized with the Golgi apparatus. The androgen receptor positive CWR22Rv1 cells expressed more myosin VI when compared with PC-3 cells and were characterized by intensive staining at the leading edge of the cytoplasm which suggested a role in cell migration. The LNCaP and VCaP cells demonstrated the most abundant androgen receptor expression and concomitantly the most intense diffuse myosin VI staining. Last, we observed a dramatically decreased expression of prostate specific antigen in LNCaP cells following stable knock-down of myosin VI using small hairpin RNA. However, preliminarily, the expression and nuclear localization of androgen receptor did not appear to be perturbed in the absence of myosin VI. These results, while mostly observational, suggest that myosin VI may engage different cellular components in different stages of prostate cancer progression, and that its role in androgen signaling warrants further study.