FREQUENT REDUCTION OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION AND CONNEXIN43 EXPRESSION IN HUMAN AND MOUSE LUNG-CARCINOMA CELLS

The reduced gap junctional intercellular communication (GJIC) and gap junction protein (connexin) expression that have been noted in many ne oplastic cell types may contribute to the neoplastic phenotype, We ass essed GJIC (by fluorescent dye micro-injection) and connexin expressio n (by Northern blotting, Western blotting and immunohistochemistry) in five mouse and 17 human lung carcinoma cell lines; both measures were lower in neoplastic cells compared to non-transformed lung epithelial cells, Other connexins were not detected in these cells. Go-culture e xperiments indicated that carcinoma cell lines able to transfer dye am ong themselves (homologous GJIC) had little capacity for dye-coupling with non-transformed cells (heterologous GJIC). Southern blot analyses indicated that reductions in GJIC and connexin43 expression were not due to deletions or rearrangements of this gene, but were more likely accounted for by transcriptional downregulation and/or post-transcript ional factors. No correlations between GJIC and known oncogene and tum or suppressor gene alterations in the human lung carcinoma cells were apparent, suggesting that other mechanisms down-regulate GJIC in these cells, Since the neoplastic cell lines exhibited low GJIC (either hom ologous or heterologous), this characteristic may be involved in expre ssion of the neoplastic phenotype.