Restored gap junctional communication in non-tumorigenic HeLa-normal human fibroblast hybrids

Abstract

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.

CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells

“…Their study found HepG2, HeLa and HEK-293T cells supporting reduced levels of cell-to-cell transmission. It is likely that the CMFDA diffusion in these cells is impaired as they, unlike Huh7, contain low numbers of gap junctions or none at all (Carruba et al , 2004; Clayton et al , 2005; de Feijter-Rupp et al , 1998; Stong et al , 2006). In our co-culture system, we found no evidence for passive diffusion of EGFP from recipient to donor cells (Fig.…”

Gap junction expression following UVC-induced neoplastic transformation in human hybrid cell lines

“…The role of GJIC in the neoplastic transformation of these hybrid cells has not been studied in detail. There is evidence for loss of homologous coupling in a spontaneously arising tumorigenic segregant and this was associated with loss of expression of connexin43 at the mRNA and protein levels (36). In the present study we have examined the status of homologous and heterologous GJIC in a UVC-induced tumorigenic HeLaϫskin fibroblast cell line, as well as its revertants with less aggressive tumorigenic phenotypes.…”

Inhibition of gap junctional intercellular communication in rat liver epithelial cells with transforming RNA

“…On the other hand, normal cells, exposed to tumor promoting agents, and malignant tumor cells are frequently characterized by reversible‐ or stable‐disrupted GJIC, respectively [1,2]. Thus, the disruption of GJIC has been hypothesized to overcome the suppression of initiated cells by the surrounding normal cells and to allow the clonal expansion of preneoplastic cells, leading to an idea that the Cx genes belong to a family of tumor suppressor genes [12–15]. Combined with these observations, we expect that the transforming RNA3S + would also suppress the translation of gap junction proteins which would lead to the inhibition of GJIC.…”