Restored gap junctional communication in non-tumorigenic HeLa-normal human fibroblast hybrids.
Gap junctional intercellular communication (GJIC) has been implicated in homeostasis, development, differentiation, wound healing or regeneration and adaptive responses of differentiated cells. The dysfunction of homologous or heterologous GJIC has been associated with the tumorigenic phenotype. Restoration of growth control and the suppression of the tumorigenic phenotype have been previously associated with the up-regulation of GJIC by various anti-tumorigenic chemicals or transfection of connexin genes into tumor cells. To test the hypothesis that 'tumor suppressor' genes may be associated with the up-regulation of GJIC, we tested clones of tumorigenic HeLa, several non-tumorigenic HeLa-normal human fibroblast somatic cell hybrids and a tumorigenic segregant of one of the non-tumorigenic hybrids for GJIC. The parental HeLa cells (D98 AH.2) had no detectable GJIC but expressed detectable connexin 43 transcripts, while the non-tumorigenic HeLa-human fibroblast hybrids, which contained the chromosome 11 from the normal human fibroblast (CGL-1, CGL-2, ESH15 and EHS15c1), expressed ample connexin 43 transcripts and showed proficient GJIC. The tumorigenic segregant (CGL-3) from 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-human fibroblast hybrid and further suggest that GJIC may be associated with the mechanisms of tumor suppression. The mechanism by which the tumor suppressor gene(s) on the normal chromosome in the HeLa-human fibroblasts induces the up-regulation of connexin 43 is not yet explained.
de Feijter-Rupp
H L
HL
Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing 48824, USA.
Hayashi
T
T
Kalimi
G H
GH
Edwards
P
P
Redpath
J L
JL
Chang
C C
CC
Stanbridge
E J
EJ
Trosko
J E
JE
D001483:Base Sequence; D002450:Cell Communication; D018031:Connexin 43 / Q000378:metabolism; D017931:DNA Primers; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D017629:Gap Junctions; D006367:HeLa Cells; D006801:Humans; D006822:Hybrid Cells; D007546:Isoquinolines; D008845:Microinjections
D018031:Connexin 43; D017931:DNA Primers; D005456:Fluorescent Dyes; D007546:Isoquinolines; C017475:lucifer yellow