Tumour promoters enhance anchorage-independent growth of adenovirus-transformed cells without altering the integration pattern of viral sequences

Abstract

Carcinogenesis often involves interaction between multiple factors and proceeds through several discrete steps^1–8. In mouse skin two distinct phases, ‘initiation’ and ‘promotion’, have been described². The most potent tumour-promoting agents in mouse skin are 12-O-tetradecanoylphorbol-13-acetate (TPA) and related diterpenes^3–5. A significant experimental advance in studies on the mechanism of action of tumour promoters has been the demonstration that they induce specific biochemical and biological effects in cell culture^6–8. These effects include phenotypic changes that mimic those seen during transformation; modulation of differentiation; enhancement of the expression of markers of transformation in cells that are already transformed; and an increased yield of transformed foci in cultures exposed to chemical carcinogens or radiation^6–11. We have previously reported that TPA also increases the yield of transformed foci in rat embryo cultures previously infected with a mutant of type 5 adenovirus¹². When foci of adenovirus-transformed cells are picked, cloned and serially passaged, they undergo progressive changes, the most notable of which is acquisition of anchorage-independent growth¹³. The present study demonstrates that although TPA enhances the acquisition of anchorage-independent growth in adenovirus-transformed cells (and not in normal cells), this alteration in growth properties is not due to a change in the integration pattern of adenovirus DNA sequences in the genome of the host cell.