Laminin-5-mediated gene expression in human prostate carcinoma cells

Interactions between extracellular matrix (ECM) proteins and prostate carci noma cells provide a dynamic model of prostate tumor progression. Previous work in our laboratory showed that laminin-5, an important member of a fami ly of ECM glycoproteins expressed in the basal lamina, is lost in prostate carcinoma. Moreover, we showed that the receptor for laminin-5, the alpha6 beta4 integrin, is altered in prostate tumors. However, the genes that lami nin-5 potentially regulates and the significance of its loss of expression in prostate cancer are not known. We selected cDNA microarray as a comprehe nsive and systematic method for surveying and examining gene expression ind uced by laminin-5. To establish a definitive role for laminin-5 in prostate tumor progression and understand the significance of its loss of expressio n, we used a cDNA microarray containing 5289 human genes to detect perturba tions of gene expression when DU145 prostate carcinoma cells interacted wit h purified laminin-5 after 0.5, 6, and 24 h. Triplicate experiments showed modulations of four, 61, and 14 genes at 0.5, 6, and 24 h, respectively. Ge nes associated with signal transduction, cell adhesion, the cell cycle, and cell structure were identified and validated by northern blot analysis. Pr otein expression was further assessed by immunohistochemistry. (C) 2001 Wil ey-Liss, Inc.