The interaction of the tumor cell with its extracellular matrix may play an important role in determining its metastatic and invasive properties. We have identified, isolated, and characterized cDNA clones of the human and the mouse 37 kDa laminin receptor precursor (37LRP) of the 67 kDa high affinity laminin receptor (67LR). The 67LR is expressed to a greater degree in metastatic tissues than in benign conditions in a variety of tissue-specific neoplasms. The 37LRP contains a laminin binding site that is conserved throughout evolution in organisms that either synthesize or bind to laminin. Prokaryotic and invertebrate homologs of the 37LRP have ribosome binding activity. It is presumed that vertebrate 37LRP proteins are multifunctional with both laminin- and ribosome-binding properties. The human and chicken 37LRP genes were recently cloned and analyzed. Human and chicken genes have the same exon-intron structure. The human gene was localized to chromosome 3p, band 21 and contains 7 exons that span 6 kb. The 5 region that flanks exon 1 does not contain a TATA box but contains other regulatory motifs including five Sp1 sites, a glucocorticoid responsive element, an AP1 site, and a metal responding element. Intron 1 is GC rich and contains seven Sp1 sites, suggesting it may participate in the regulation of 37LRP gene expression. Indeed, recent evidence from reporter gene transfection experiments demonstrates negative transcriptional regulatory elements within intron 1. Like many genes that encode ribosome binding proteins, intron 4 of the human gene contains the full sequence for a small nucleolar RNA. The introduction of 37LRP antisense constructs into metastatic cancer cells resulted in a shortened half- life of the sense mRNA and also decreased cell motility and attachment to laminin. These data are consistent with the model that the 37LRP is a precursor to a cell surface laminin binding protein, in addition to its function in the ribosome. - cancer, chromosome, transcriptional control, transgenic mice,
