Investigation into the mechanism of the loss of laminin 5 (alpha 3 beta 3 gamma 2) expression in prostate cancer

Laminin 5 is a pivotal hemidesmosomal protein involved in cell stability, m igration, and anchoring filament formation. Protein and gene expression of the alpha3, beta3, and gamma2 chains of laminin 5 were investigated in norm al and invasive prostate carcinoma using immunohistochemistry, Northern ana lysis, and in situ hybridization. Laser capture microdissection of normal a nd carcinomatous glands, in conjunction with RNA amplification and reverse Northern analysis, were used to confirm the gene expression data. Protein a nd mRNA expression of all three laminin 5 chains were detected in the basal cells of normal glands. Ln contrast, invasive prostate carcinoma showed a loss of beta3 and gamma2 protein expression with variable expression of a3 chains. Despite the loss of protein expression, there was retention of beta 3 and gamma2 mRNA expression as detected by in situ hybridization, Northern and reverse Northern analysis. Our findings imply that an altered mechanis m of translation of beta3 or gamma2 mRNAs into functional proteins contribu tes to failure of anchoring filaments and hemidesmosomal formation. The res ultant hemidesmosome instability or loss would suggest a less stable epithe lial-stromal junction, increased invasion and migration of malignant cells, and disruption of normal integrin signaling pathways.