Carcinogenesis, Vol 19, 747-754, Copyright © 1998 by Oxford University Press
HL de Feijter-Rupp, T Hayashi, GH Kalimi, P Edwards, JL Redpath, CC Chang, EJ Stanbridge and JE Trosko
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.
ARTICLES
Restored gap junctional communication in non-tumorigenic HeLa-normal human fibroblast hybrids
Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing 48824, USA.
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