Date of Award
Doctor of Philosophy
Mouse mammary tumor virus (MMTV) is a retrovirus which causes mammary tumors in many strains of mice. An essential part of the viral life cycle involves the integration of a double-stranded DNA provirus into the host cell genome. Tumorigenesis is thought to be mediated by such integrated proviruses.;Restriction endonuclease analysis of the DNA from a series of cell sublines from a single MMTV-induced mammary adenocarcinoma revealed that the original tumor was composed of tumorigenic and nontumorigenic cells whose proviral content could not be correlated with tumorigenicity. The tumorigenic sublines however contained a single provirus which was correlated with tumorigenicity. The tumorigenic potential of MMTV proviruses therefore depends on the site of integration.;In a second study it was shown that the mode of action of a germinally-transmitted locus of GR mice, Mtv-2, was through the generation of proviruses which activated the putative mammary proto-oncogenes int-1 and int-2.;It was also shown that a series of chemically or hormonally induced hyperplastic alveolar nodule outgrowth lines each had an integrated MMTV provirus at the same site in the genome. This locus was shown to be different from the putative mammary proto-oncogenes int-1 and int-2. Since this locus is associated with hyperplasia (a preneoplastic condition), it has been designated int-H.;A portion of the int-H locus was molecularly cloned in a lamba phage vector-host system designed to prevent the deletion of those sequences capable of forming secondary structures. DNA from the int-H region has homology to a family of sequences in rat and human as well as mouse DNA. Transcripts from this region were detected in normal midpregnant mammary tissue as well as in preneoplastic tissue. This locus may code for a regulatory molecule. Proviral disruption of int-H regulation may predispose cells to becoming tumorigenic.
Gray, Douglas Andrew, "The Role Of Mouse Mammary Tumor Virus In The Induction And Progression Of Mouse Mammary Tumors" (1986). Digitized Theses. 1495.