Effect of retroviral integration on control of expression of a tumor marker in HeLa cells

Fusion between HeLa cells and normal human fibroblasts results in the suppression of tumorigenicity. Under prolonged culture conditions, rare tumorigenic segregants arise and have been shown to reexpress a cell surface antigen, p75, which is also present in the HeLa parent but not in the fibroblast parent or in the nontumorigenic HeLa x fibroblast hybrid. Expression of p75 strictly correlates with tumorigenicity in HeLa and human somatic cell hybrids, as has been shown by chromosomal segregation and after gamma-irradiation. Using insertional mutagenesis, we induced expression of p75 in the nontumorigenic hybrid. Three cell clones were isolated that expressed p75 at different levels. Two of these clones exhibited a high level of p75 expression and displayed an altered morphology similar to that of the previously characterized tumorigenic segregants and consistent with the appearance of tumorigenicity. When injected into athymic nude mice, two clones were found to be tumorigenic, one from the onset of subculturing and the second only after further propagation for approximately 50 population doublings. The third clone showed very low p75 expression, had no altered morphology, and was nontumorigenic.