BETA(4) INTEGRIN SUBUNIT EXPRESSION IS DOWN-REGULATED IN LOW METASTATIC CARCINOMA VARIANTS

Organization and expression of the gene coding for beta(4) integrin su bunit were investigated in murine carcinoma lines endowed with low and high metastatic potential maintained both in vivo and in vitro. Probe s corresponding to either the extracellular or the cytoplasmic domains of the protein were generated and employed for Southern and Northern blot hybridization experiments. Southern blot analysis demonstrates a restriction fragment-length polymorphism between BALB/c and C57BI/6J D NAs. The different genomic organization of the beta(4) gene apparently does not generate variation in mRNA length. Northern blot analysis re veals a 7-kb transcript encoding full-length beta(4) protein and short er transcripts that apparently correspond to nonfunctional mRNAs. In c arcinoma cells endowed with low metastatic capacity, the 7-kb mRNA can not be revealed in spite of the presence of shorter transcripts. In co ntrast, the 7-kb transcript is always present in tumor cells endowed w ith high metastatic capacity. Accordingly, the beta(4) protein is dete ctable, either by immunofluorescence or by Western blot analyses, only in highly metastatic carcinoma cells. In conclusion, the data present ed show that in these murine carcinoma cell line (i) the 7-kb mRNA is associated with a more invasive phenotype, and (ii) missing expression of the beta(4) integrin subunit in low metastatic carcinoma cells dep ends, at least in part, on mechanisms acting at a post-transcriptional level. The possibility that beta(4) subunit expression is a consequen ce of specific differentiation stages of lung carcinoma cells is discu ssed.