RESTORED GAP JUNCTIONAL COMMUNICATION IN NONTUMORIGENIC HELA-NORMAL HUMAN FIBROBLAST HYBRIDS

Gap junctional intercellular communication (GJIC) has been implicated in homeostasis, development, differentiation, wound healing or regener ation and adaptive responses of differentiated cells. The dysfunction of homologous or heterologous GJIC has been associated with the tumori genic phenotype, Restoration of growth central and the suppression of the tumorigenic phenotype have been previously associated with the up- regulation of GJIC by various anti-tumorigenic chemicals or transfecti on of connexin genes into tumor cells. To test the hypothesis that 'tu mor suppressor' genes may be associated with the up-regulation of GJIC , we tested clones of tumorigenic HeLa, several non-tumorigenic HeLa-n ormal human fibroblast somatic cell hybrids and a tumorigenic segregan t of one of the non-tumorigenic hybrids for GJIC, The parental HeLa ce lls (D98 AH.2) had no detectable GJIC but expressed detectable connexi n 43 transcripts, while the non-tumorigenic HeLa-human fibroblast hybr ids, which contained the chromosome 11 from the normal human fibroblas t (CGL-1, CGL-2, ESH15 and EHS15c1), expressed ample connexin 43 trans cripts and showed proficient GJIC, The tumorigenic segregant (CGL-3) f rom the non-tumorigenic HeLa-human fibroblast hybrid showed no GJIC or connexin 43. These results show that the presence of GJIC is closely linked to the suppression of the tumorigenic phenotype in the HeLa-hum an fibroblast hybrid and further suggest that GJIC may be associated w ith the mechanisms of tumor suppression. The mechanism by which the tu mor suppressor gene(s) on the normal chromosome in the HeLa-human fibr oblasts induces the up-regulation of connexin 43 is not yet explained.