Examination of the oncogenic potential of H19 gene in HeLa x normal human fibroblast hybrid cells

Fusion of tumorigenic HeLa cells with human skin fibroblasts results in chr omosomally stable non-tumorigenic hybrids. The studies of rare spontaneous tumorigenic segregants from the non-tumorigenic hybrid have implicated the loss of one copy of human fibroblast chromosome 11 with concomitant re-expr ession of tumorigenicity. In a previous study of differential display scree ning, we reported the tumorigenic-specific expression of H19 gene as a poss ible candidate for elicitation of tumorigenic phenotype. In this study, we examined the expression of H19 gene using gamma -ray-induced tumorigenic mu tants (GIMs) and non-tumorigenic irradiated control cells (CONs) from the n on-tumorigenic hybrids. H19 expression was recognized in all the GIMs with various expression levels, whereas no CONs expressed the H19 gene. To exami ne the tumorigenic potentials of H19 gene directly, we introduced an H19 ge ne expression vector into the non-tumorigenic hybrids and assayed the tumor igenicity of the transfectants by s.c. injection into athymic nude mice. Ho wever, no transfectants with stable H19 gene expression induced in vivo tum or growth. These results suggest that expression of the H19 gene may be nec essary but is not sufficient to confer the tumorigenic phenotype in HeLa x fibroblast hybrids.