Abstract
Carcinogenesis often involves interaction between multiple factors and proceeds through several discrete steps1–8. 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 diterpenes3–5. 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 culture6–8. 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 radiation6–11. 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.
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Fisher, P., Dorsch-Häsler, K., Weinstein, I. et al. Tumour promoters enhance anchorage-independent growth of adenovirus-transformed cells without altering the integration pattern of viral sequences. Nature 281, 591–594 (1979). https://doi.org/10.1038/281591a0
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DOI: https://doi.org/10.1038/281591a0
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