Abstract
Abstract : In order to better understand how polarized membrane trafficking pathways change during the loss of epithelial cell polarity during cancer progression we have studied syntaxins 3 and 4 in prostate cancer. Tumors of different stages from a TRAMP mice, human prostate cancers, and human prostate cancer cell lines were investigated for the expression and subcellular localization of syntaxins 3 and 4 by confocal microscopy and Western blot analysis. Like in renal epithelial cells, syntaxins 3 and 4 are strictly localized to the apical and basolateral plasma membrane, respectively, in normal human and mouse prostate epithelial cells. The expression of syntaxin 3 and syntaxin 4 in the plasma membrane were down-regulated in the tumor cells of Tramp mice and human prostate cancers, although they were still localized apically, basolaterally, respectively in tumor cells, in which the cell polarity was preserved. In contrast, syntaxins 3 and 4 were mislocalized to intracellular vesicles in metastatic prostate cancer cells. The mislocalization was also observed in human prostate cancer cell line DU145 when the cell polarity lost when the cells were cultured in low calcium medium. These results suggest that loss of epithelial cell polarity during cancer progression involves major changes in polarized exocytic pathways.
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