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American Journal of Pathology, Vol 149, 1341-1349, Copyright © 1996 by American Society for Investigative Pathology

REGULAR ARTICLES

Differential expression of laminin 5 (alpha 3 beta 3 gamma 2) by human malignant and normal prostate

J Hao, Y Yang, KM McDaniel, BL Dalkin, AE Cress and RB Nagle
Department of Pathology, Arizona Cancer Center, University of Arizona, Tucson, USA.

Laminin 5 is an extracellular matrix protein integral to the formation of the hemidesmosomes that attach normal basal cells to the underlying basal lamina. We have shown that these hemidesmosomal complexes are lost in prostate carcinoma, possibly allowing malignant cells to detach from the anchoring structures and then to invade and migrate through the adjacent tissue. Our previous immunohistochemical studies of normal and malignant human prostate tissue demonstrated that the laminin subchains alpha 1, alpha 2, beta 1, beta 2, gamma 1, and gamma 2 were all expressed as normal components of the basal lamina surrounding prostate glands. Although most of these subchains were also expressed by the de novo basal lamina synthesized by prostate carcinoma, the gamma 2 subchain of laminin 5 was not detected. In an effort to investigate the role laminin 5 plays in the tumorigenesis of prostate carcinoma, the protein expression of the three subchains of laminin 5 (alpha 3, beta 3, and gamma 2) was compared in normal prostate, prostatic intraepithelial neoplasia, and invasive carcinoma using immunohistochemistry. The results showed that the protein for the alpha 3 subchain of laminin 5 is retained by both normal prostate epithelium and prostate carcinoma, but the beta 3 and the gamma 2 subchains were not detected in invasive carcinoma. Despite the absence of the gamma 2 protein, however, the carcinoma cells continued to express substantial amounts of the gamma 2 mRNA. Although it is unclear how the gene for the gamma 2 subchain of laminin 5 is regulated, results of this study suggest that there is a post-transcriptional defect in the expression of the gamma 2 subchain that occurs during the progression from a premalignant lesion to invasive carcinoma. As laminin 5 is a component of the anchoring filaments, the failure to express the gamma 2 subchain may contribute to the failure to form anchoring filaments and hemidesmosomes. This failure of hemidesmosome formation results in a less stable epithelial-stromal junction, which may allow malignant cells more potential to invade and spread through adjacent structures.

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