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Phorbol ester-mediated stimulation of the synthesis of mouse mammary tumour virus

Abstract

12-O-tetradeconoyl-phorbol-13-acetate (TPA) is a potent tumour promoter in the two-stage mouse skin carcinogenesis model1,2. Recently, TPA has been shown to enhance the transformation of cultured cells by two DNA tumour viruses—adenovirus3 and Epstein–Barr virus4. It is not known whether TPA also augments the transformation of cells by RNA tumour viruses. In Rous sarcoma virus (type C) transformed fibroblasts, the levels of plasminogen activator are elevated by TPA5,6, a phenomenon also associated with malignant transformation7,8. In addition, TPA and other promoters induce the synthesis of some herpesviruses in persistently infected cells9,10. I have investigated the effect of TPA on the synthesis of mouse mammary tumour virus (MMTV), type B RNA tumour virus, and find that TPA, in nanogramme quantities, causes a 10- to 20-fold stimulation of MMTV production by persistently infected mouse mammary tumour cells. This stimulation is specific for TPA; the non-promoter, phorbol, does not stimulate MMTV production.

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