Biomaterial Database

Activation of int-1 and int-2 mammary oncogenes in hormone-dependent and -independent mammary tumors of GR mice. 1987

J Mester, and E Wagenaar, and M Sluyser, and R Nusse

Mammary tumors in the GR mouse strain are caused by the expression of an endogenous provirus of the mouse mammary tumor virus (MMTV). The tumors progress from a hormone-dependent growth phase to autonomous, hormone-independent growth. We studied proviral insertion of MMTV at the int-1 and int-2 mammary oncogenes and the transcription of these genes during progression of a series of transplanted mammary tumors. During the hormone-dependent phase, 6 of 15 transplanted tumors were positive for proviral insertion at int-1 or int-2 or both. These tumors were oligoclonal with respect to the fraction of tumor cells with novel int-1 and int-2 restriction fragments and, apparently, consisted of different tumor cells with proviruses integrated at different oncogenes, including genes that are not yet known. In 10 tumors we detected expression of the int genes, indicating that most tumors contain minor populations of cells with int-1 or int-2 activations. On transplantation the tumors remained oligoclonal during the hormone-dependent phase. The hormone-independent variants of the tumors emerged as clonal outgrowths of cells with MMTV proviruses that could be traced back in the hormone-dependent tumors, but not always those of cells that were positive for insertions near int-1 or int-2. The maintenance of oligoclonality during the hormone-dependent phase suggests a growth-controlling effect of different populations of cells on each other. The clonal, hormone-independent tumors that arise later seem to be the result of mutations that are unrelated to int activation.

UI	MeSH Term	Description	Entries
D008324	Mammary Tumor Virus, Mouse	The type species of BETARETROVIRUS commonly latent in mice. It causes mammary adenocarcinoma in a genetically susceptible strain of mice when the appropriate hormonal influences operate.	Bittner Virus,Mammary Cancer Virus,Mouse mammary tumor virus,Mammary Tumor Viruses, Mouse
D008325	Mammary Neoplasms, Experimental	Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.	Experimental Mammary Neoplasms,Neoplasms, Experimental Mammary,Experimental Mammary Neoplasm,Mammary Neoplasm, Experimental,Neoplasm, Experimental Mammary
D008815	Mice, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.	Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009857	Oncogenes	Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.	Transforming Genes,Oncogene,Transforming Gene,Gene, Transforming,Genes, Transforming
D010052	Ovariectomy	The surgical removal of one or both ovaries.	Castration, Female,Oophorectomy,Bilateral Ovariectomy,Bilateral Ovariectomies,Castrations, Female,Female Castration,Female Castrations,Oophorectomies,Ovariectomies,Ovariectomies, Bilateral,Ovariectomy, Bilateral
D002455	Cell Division	The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.	M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D004262	DNA Restriction Enzymes	Enzymes that are part of the restriction-modification systems. They catalyze the endonucleolytic cleavage of DNA sequences which lack the species-specific methylation pattern in the host cell's DNA. Cleavage yields random or specific double-stranded fragments with terminal 5'-phosphates. The function of restriction enzymes is to destroy any foreign DNA that invades the host cell. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms. They are also used as tools for the systematic dissection and mapping of chromosomes, in the determination of base sequences of DNAs, and have made it possible to splice and recombine genes from one organism into the genome of another. EC 3.21.1.	Restriction Endonucleases,DNA Restriction Enzyme,Restriction Endonuclease,Endonuclease, Restriction,Endonucleases, Restriction,Enzymes, DNA Restriction,Restriction Enzyme, DNA,Restriction Enzymes, DNA
D005260	Female		Females
D005814	Genes, Viral	The functional hereditary units of VIRUSES.	Viral Genes,Gene, Viral,Viral Gene
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia