Int-6, a highly conserved, widely expressed gene, is mutated by mouse mammary tumor virus in mammary preneoplasia
| Autor: | Gilbert H. Smith, Robert Callahan, S Miyazaki, F Buttitta, D Gallahan, A Marchetti |
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| Rok vydání: | 1995 |
| Předmět: |
Gene Expression Regulation
Viral Eukaryotic Initiation Factor-3 Virus Integration viruses Molecular Sequence Data Restriction Mapping Immunology Mutagenesis (molecular biology technique) Biology Microbiology Gene product Mice Proviruses Mammary tumor virus Proto-Oncogene Proteins Sequence Homology Nucleic Acid Virology Animals Amino Acid Sequence RNA Messenger RNA Neoplasm Cloning Molecular Gene Regulation of gene expression Mammary tumor Base Sequence Mouse mammary tumor virus Intron Mammary Neoplasms Experimental Cell Transformation Viral biology.organism_classification Molecular biology Mutagenesis Insertional Genes Mammary Tumor Virus Mouse Insect Science Mutation Precancerous Conditions Research Article |
| Zdroj: | Journal of Virology. 69:1932-1938 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.69.3.1932-1938.1995 |
| Popis: | With a unique mouse mammary tumor model system in which mouse mammary tumor virus (MMTV) insertional mutations can be detected during progression from preneoplasia to frank malignancy, including metastasis, we have discovered a new common integration site (designated Int-6) for MMTV in mouse mammary tumors. MMTV was integrated into Int-6 in a mammary hyperplastic outgrowth line, its tumors and metastases, and two independent mammary tumors arising in unrelated mice. The Int-6 gene is ubiquitously expressed as a 1.4-kb RNA species in adult tissues and is detected beginning at day 8 of embryonic development. The nucleotide sequence of Int-6 is unrelated to any of the known genes in the GenBank database. MMTV integrates within introns of the gene in the opposite transcriptional orientation. In each tumor tested, this results in the expression of a truncated Int-6/long terminal repeat (LTR) chimeric RNA species which is terminated at a cryptic termination signal in the MMTV LTR. Since the nonrearranged Int-6 alleles in these tumors contain no mutations, we favor the conclusion that truncation of the Int-6 gene product either biologically activates its function or represents a dominant-negative mutation. |
| Databáze: | OpenAIRE |
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