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Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer
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Concerted activation of two potential proto-oncogenes in carcinomas induced by mouse mammary tumour virus

G Peters, A E Lee, C Dickson

    Nature
    |April 17, 1986
    PubMed

    Insights

    Mouse mammary tumor virus (MMTV) can activate cellular proto-oncogenes int-1 and int-2, potentially acting as oncogenes in mammary carcinoma development. Further research is needed to understand other contributing factors.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Virology

    Background:

    • Retroviruses lacking oncogenes can induce tumors by activating cellular proto-oncogenes.
    • The int-1 and int-2 genes are identified as common targets for activation by mouse mammary tumor virus (MMTV).

    Purpose of the Study:

    • To investigate the transcriptional activity and structural integrity of int-1 and int-2 loci in BR6 mouse mammary tumors.
    • To determine the role of int-1 and int-2 activation in mammary carcinogenesis.

    Main Methods:

    • Analysis of proviral insertion and gene expression in 30 BR6 mouse mammary tumors.
    • Assessment of transcriptional activity and structural integrity of int-1 and int-2 loci.

    Main Results:

    • Approximately 50% of tumors showed expression of both int-1 and int-2 genes.
    • Activation of these genes occurred in ostensibly monoclonal cell populations.
    • Three tumors (10%) did not involve int-1 or int-2, and five cases showed activation without adjacent provirus.

    Conclusions:

    • int-1 and int-2 may act cooperatively in mammary carcinoma genesis.
    • Other loci and mechanisms contribute to tumorigenesis, indicating a complex process.

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