Genetics of mouse mammary tumor virus-induced mammary tumors: linkage of tumor induction to the gag gene.

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Animal, Female, Gene-Expression-Regulation-Neoplastic, Gene-Expression-Regulation-Viral, Genes-gag, Mammary-Neoplasms-Experimental, Mammary-Tumor-Viruses-Mouse, Mice, Mice-Inbred-C3H, Molecular-Sequence-Data, Sequence-Alignment, SUPPORT-U-S-GOVT-P-H-S

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J Virol 2000 Oct; 74(19):8876-83.


CA65795/CA/NCI, CA45954/CA/NCI, CA34196/CA/NCI


Retroviruses are believed to induce tumors by acting as insertional mutagens that activate expression of cellular protooncogenes. Indeed, almost 90% of mouse mammary tumor virus (MMTV)-induced mammary tumors in C3H/He mice show upregulation of Int protooncogenes. We have analyzed three different MMTV variants [MMTV(C3H), MMTV(HeJ), and a genetically engineered MMTV hybrid provirus (HP)] for tumorigenicity in mice from two distinct genetic backgrounds. All three viruses were tumor causing in BALB/cJ mice. However, only MMTV(C3H), but not MMTV(HeJ) or HP, induced mammary tumors in C3H/He mice. All of the viruses were infectious on either background and up-regulated expression of Int genes in tumors they induced. Like HP, MMTV(HeJ) was found to be a genetic recombinant between endogenous Mtv1 provirus and exogenous MMTV(C3H). Sequence comparison of MMTV variants linked the tumorigenicity of MMTV(C3H) to the gag region of the retrovirus.

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