Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15

  title={Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15},
  author={Roel Nusse and Albert van Ooyen and David R. Cox and Yuen Kai T Fung and Harold Varmus},
Most mammary carcinomas induced in C3H mice by the mouse mammary tumour virus (MMTV) bear a new proviral insertion within a highly conserved locus on chromosome 15 called int-1. A transcriptional unit within this locus is inactive in all tested normal tissues but expressed at low levels in mammary tumours with proviral insertions positioned on either the 5′ and 3′ sides of the gene. Transcription of the proviruses proceeds away from int-1; thus an indirect mechanism appears to activate… 
A putative int domain for mouse mammary tumor virus on mouse chromosome 7 is a 5' extension of int-2
An additional example of proviral integration is described in which a provirus in a presumed enhancer-insertion mode 15 kilobases upstream of the int-2 promoters is capable of activating expression of the gene at levels typical of other virally induced mammary tumors.
Concerted activation of two potential proto-oncogenes in carcinomas induced by mouse mammary tumour virus
The data suggest that int-1 and int-2 may act cooperatively in the genesis of mammary carcinomas, and because in five cases activation occurred in the apparent absence of an adjacent provirus, it is clear that other loci and mechanisms contribute to tumorigenesis.
The activation of cellular oncogenes by proviral insertion in murine mammary cancer.
  • R. Nusse
  • Biology
    Cancer treatment and research
  • 1988
In this chapter, I shall review our current knowledge of the mechanism of mammary oncogenesis by the Mouse Mammary Tumor Virus (MMTV), with particular emphasis on the activation of cellular oncogenes
The Role of Specific Regions for Proviral Integration in Mouse Mammary Tumor Virus (MMTV) Induced Tumors
In the workshop entitled “Viruses and Oncogenes” an effort was made to summarize the current knowledge on specific chromosomal regions involved in MMTV-induced mammary tumor formation. Two such
Retroviral insertional mutagenesis in murine mammary cancer
It is proposed that int-1 is a cellular oncogene for mammary tumours, which encodes a protein that is highly conserved between mouse and man and is presumably caused by the transcriptional enhancer present on the MMTV long terminal repeat.
Molecular cloning and chromosomal assignment of the human homolog of int-1, a mouse gene implicated in mammary tumorigenesis
The human homolog of this putative mammary oncogene is cloned and its structure is compared to that of the mouse gene by heteroduplex analysis.


Multiple arrangements of viral DNA and an activated host oncogene in bursal lymphomas
Activation of adjacent cellular genes by retroviral DNA can involve mechanisms other than provision of a transcriptional promoter in the vicinity of a putative cellular oncogene.
Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis
The data indicate that, as a rare event, the ALV provirus integrates adjacent to the c-myc gene and that transcription, initiating from a viral promoter, causes enhanced expression of c- myc, leading to neoplastic transformation.
Nucleotide sequences at host–proviral junctions for mouse mammary tumour virus
Proviruses cloned from rat cells infected with mouse mammary tumour virus, a B-type retrovirus regulated by glucocorticoid hormones, show the structural features of transposable elements: short
Subfragments of the large terminal repeat cause glucocorticoid-responsive expression of mouse mammary tumor virus and of an adjacent gene.
A MMTV LTR-thymidine kinase (tk) chimeric gene is constructed and the biological activity of molecules containing various deletions in the LTR after transformation of LTK- APRT- mouse cells is tested.
Mouse c-myc oncogene is located on chromosome 15 and translocated to chromosome 12 in plasmacytomas.
Hybridization studies with viral oncogene probes indicate that c-myc, the cellular gene homologous to the transforming gene of avian myelocytomatosis virus, resides on mouse chromosome 15 and in many
A common region for proviral DNA integration in MoMuLV-induced rat thymic lymphomas
MoMuLV-induced rat thymic lymphomas are generated and their clonal nature is confirmed and there is indeed a cellular DNA region (termed the ML VI-1 locus) that serves as the substrate for proviral DNA integration in 5 out of 16 tumours the authors examined.
A small region of the mouse mammary tumor virus long terminal repeat confers glucocorticoid hormone regulation on a linked heterologous gene.
  • J. Majors, H. Varmus
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1983
The results show that 290 base pairs of the MMTV LTR are sufficient to confer regulation on the downstream gene, and that the distance between the putative signal for hormone response and the start site of transcription can be varied without affecting regulation.