ROLE OF GAP-JUNCTIONS IN LUNG NEOPLASIA

Reduced gap junctional intercellular communication (GJIC) has been not ed in many types of neoplastic cells and may contribute to the neoplas tic phenotype. This study assessed GJIC (by fluorescent dye-coupling) and gap junction protein (connexin) expression in mouse and human lung carcinoma cell lines and investigated whether reduced GJIC was involv ed in their neoplastic phenotype. Dye-coupling and connexin43 (Cx43) e xpression were much lower in most of the carcinoma lines (16 of 22) co mpared to nontransformed lung epithelial cells. Other connexins were n ot detected. A poorly communicating mouse lung carcinoma cell line (E9 ) was transfected with Cx43 or transduced with Cx32 and several stable clones were isolated that had 2- to 4-fold increased dye coupling. Wh en evaluated for growth in vitro, the population doubling times were i ncreased and the saturation densities were decreased in the clones. Wh en assessed for tumorigenicity, the parental E9 cells formed tumors wi th a 100% incidence (6/6 mice), whereas the clones varied in tumorigen ic response (0-88% incidence). The best communicating clone (E9-2) was not tumorigenic. The highly communicating Cx32 clone, E9/32-9, gave a tumor incidence of 88%. These results suggest that restoration of GJI C by forced connexin expression can reduce the growth and tumorigenici ty of lung carcinoma cells in a connexin-specific manner.