Abstract
MURINE SARCOMA VIRUS (MSV)-transformed cells lack available receptors for epidermal growth factor (EGF)1,2. We have shown that this altered phenotype is the result of the endogenous production of growth factors by the MSV-trans-formed cells themselves. The major activity, isolated and purified from transformed cells, has been found in a 12,000-molecular weight peak and competed with EOF in an EGF-receptor-binding assay3. This growth factor, called sarcoma growth factor (SGF), stimulates cell division, causes normal cells to grow in soft agar and produces rapid, reversible morphological transformation of cells in monolayer culture3. There is no evidence that SGF acts as a complete carcinogen, producing permanent cell transformation; its properties resemble classical chemical promoters of carcinogenesis, like 12-O-tetradecanoylphorbol-13-acetate (TPA)4–6, the highly active component of croton oil. Whereas TPA is an exogenous plant derivative acting on an animal or a cell, SGF is an endogenous, virally induced growth promoter. In this respect it is interesting that retinoids (vitamin A and synthetic analogues)7 block the action in vivo of exogenous and endogenous promoters, preventing carcinogens from producing new tumours, but do not reverse the growth of many established tumours7–10. Retinoids prevent cancer of the lung7,11, skin9, bladder12 and mammary gland13 in experimental animals, block cell transformation induced by chemicals14 and radiation14,15 in culture, and reverse the anchorage-independent growth of transformed mouse fibroblasts16. If SGF is part of the natural tumour-promoting system and retinoids are part of the natural defence against that system, then one should be able to demonstrate a direct antagonism in cell culture. This, report establishes that this happens.
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TODARO, G., DE LARCO, J. & SPORN, M. Retinoids block phenotypic cell transformation produced by sarcoma growth factor. Nature 276, 272–274 (1978). https://doi.org/10.1038/276272a0
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DOI: https://doi.org/10.1038/276272a0
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