Laminin alpha-1, alpha-3, and alpha-5 chain expression in human prepubertal [correction of prepubetal] benign prostate glands and adult benign and malignant prostate glands.

BACKGROUND: Laminins (Lns) are a family of extracellular matrix glycoproteins located in the basement membrane (BM) of epithelial cells. They exist as heterotrimers composed of an alpha, beta, and gamma chain. Presently, five alpha (alpha1-5), three beta (beta1-3), and three gamma (gamma1-3) chains have been identified with different combinations of these chains resulting in 14 laminin heterotrimers thus far identified (1, 3-5). METHODS: In this study, using immunohistochemistry with chain-specific antibodies, we characterized the expression of the alpha1 (Lns-1/3), alpha3 (Lns 5,6,7), and alpha5 (Lns 10/11) chains in fetal, newborn, infant, prepubertal, and adult benign and malignant prostate glands. RESULTS: In general, alpha1 expression was higher in normal fetal prostate glands and declined by full-term birth, whereas the alpha3 and alpha5 chains remained highly expressed in the adult normal glands. In carcinoma alpha1 (Lns 1/3) and alpha5 (Lns 5,6,7) are lost, whereas alpha5 (Lns 10/11) persists. CONCLUSIONS: Alpha 1 (Lns 1/3) is prominent in BM, but is replaced by a laminin matrix rich in alpha3 (Lns 5,6,7) and alpha5 (Lns 10/11) in benign adult prostate glands. In carcinoma, both alpha1 (Lns-1/3) and alpha3 (Lns 5,6,7) are not expressed with persistence of a BM rich in alpha5 (Lns 10/11).

Cell line-specific translation of two laminin 5 beta3 chain isoforms.

In sequencing the beta3 chain of laminin 5 mRNA from LNCaP cells, we observed three different human cDNA clones (XM_001716, NM_000228 and L25541) in the GenBank that identified different sequences in the untranslated regions (UTR). XM_001716 and NM_000228 are almost identical cDNA clones with approximately 99% homology. However, they are quite different from L25541 in both the 5' UTR and the 3' UTR. Development of a PCR assay to specifically detect two of these different forms of the message led to the observation that they were differentially expressed in various cell lines. The message designated B3A (NM_000228, and XM_001716) was absent in LNCaP and MCF7 and greatly reduced in PC3-N, but was present in eight other epithelial cell lines. B3B (L25541) was present in all cell lines studied. The cell lines that failed to express the B3A form also failed to express the protein based on both immunoblotting and immunohistochemical analysis. It appears from this data that there are two isoforms of the beta3 mRNA, and that the 5' UTRs of the mRNAs play an important role in regulating translation of the beta3 protein. Since laminin 5 is lost in prostate carcinoma, the mechanism of control that results in the translation of the two forms of message may be important in tumorigenesis.