Laminin alpha chains in colon carcinoma cell lines: Detection of a truncated laminin alpha 1 mRNA in Caco-2 cells

Changes in basement membrane structure are known to accompany carcinoma for mation. We analyzed laminin alpha 1 and alpha 5 chains in colon carcinoma c ell lines. Variable levels of the M-r 380,000 alpha 5 laminin protein and 1 1-kb alpha 5 laminin mRNA were noted. In contrast, laminin al protein was n ot synthesized by any of the colon carcinoma cell lines tested. Northern bl otting revealed expression of a 10-kb laminin al mRNA only in control cells . Unexpectedly, expression of a truncated laminin alpha 1 message of approx imately 8 kb was found in one cell line, the adenocarcinoma cell line Caco- 2. By RT-PCR and Northern blotting a deletion in the laminin alpha 1 mRNA w as mapped to the 5' end, spanning nucleotides 41-1835. The deletion spans t he translation start site, explaining the complete lack of the protein. Sou thern blotting of genomic Caco-2 DNA did not reveal any larger truncation, suggesting a point mutation manifested at the posttranscriptional level. Th e identified truncation is the first genetic defect described for the lamin in alpha 1 chain and suggests that mutations in the LAM gene might underlie the observed lack of the laminin al chain in some colon carcinomas. (C) 19 99 Academic Press.