DIFFERENTIAL EXPRESSION OF LAMININ-5 (ALPHA-3-BETA-3-GAMMA-2) BY HUMAN-MALIGNANT AND NORMAL PROSTATE

Laminin 5 is an extracellular matrix protein integral to the formation of the hemidesmosomes that attach normal basal cells to the underlyin g basal lamina. We have shown that these hemidesmosomal complexes are lost in prostate carcinoma, possibly allowing malignant cells to detac h from the anchoring structures and them to invade and migrate through the adjacent tissue. Our previous immunohistochemical studies of norm al and malignant human prostate tissue demonstrated that the laminin s ubchains alpha 1, alpha 2, beta 1, beta 2, gamma 1, and gamma 2 were a ll expressed as normal components of the basal lamina surrounding pros tate glands. Although most of these subchains were also expressed by t he de novo basal lamina synthesized by prostate carcinoma, the gamma 2 subchain of laminin 5 was not detected. In an effort to investigate t he role laminin 5 plays in the tumorigenesis of prostate carcinoma, th e protein expression of the three subchains of laminin 5 (alpha 3, bet a 3, and gamma 2) was compared in normal prostate, prostatic intraepit helial neoplasia, and invasive carcinoma using immunohistochemistry. T he results showed that the protein for the alpha 3 subchain of laminin 5 is retained by both normal prostate epithelium and prostate carcino ma, but the beta 3 and the gamma 2 subchains were not detected in inva sive carcinoma. Despite the absence of the gamma 2 protein, however, t he carcinoma cells continued to express substantial amounts of the gam ma 2 mRNA. Although it is unclear how the gene for the gamma 2 subchai n of laminin 5 is regulated, results of this study suggest that there is a post-transcriptional defect in the expression of the gamma 2 subc hain that occurs during the progression from a premalignant lesion to invasive carcinoma. As laminin 5 is a component of the anchoring filam ents, the failure to express the gamma 2 subchain may contribute to th e failure to form anchoring filaments and hemidesmosomes. This failure of hemidesmosome formation results in a less stable epithelial-stroma l junction, which may allow malignant cells more potential to invade a nd spread through adjacent structures.