Abstract
Mouse mammary tumour virus (MMTV) is a type B retrovirus that may be transmitted either by somatic cell infection via infectious virus borne in mother's milk or vertically by passage of virus-specific sequences in the germ line. Endogenous viral sequences act as stable genetic loci1 and are found in all inbred mouse strains studied. Available data suggest that, in general, strains exhibiting only endogenous virus have a low tumour incidence whereas a high tumour incidence occurs in strains carrying milk-borne MMTV, in addition to germ-line sequences. However, as removal of the milk-borne virus does not completely eliminate tumours, endogenous proviral sequences may also be involved in tumorigenesis2–4. Recent results have shown that proviral sequences acquired from milk are undermethylated (low 5-methylcytosine content), whereas endogenous MMTV sequences are highly methylated. An inverse relationship between proviral methylation and transcriptional activity has also been demonstrated5,6. This model suggests that an important mechanism of MMTV-induced tumorigenesis in uninfected mice (those lacking milk-borne MMTV) may involve derepression of endogenous proviruses, possibly through demethylation of these sequences. Here we show that the methylation pattern of endogenous virus sequences is specifically altered during tumorigenesis in uninfected mice.
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Breznik, T., Cohen, J. Altered methylation of endogenous viral promoter sequences during mammary carcinogenesis. Nature 295, 255–257 (1982). https://doi.org/10.1038/295255a0
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DOI: https://doi.org/10.1038/295255a0
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