PMID- 7853537 OWN - NLM STAT- MEDLINE DCOM- 19950313 LR - 20200724 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 69 IP - 3 DP - 1995 Mar TI - Int-6, a highly conserved, widely expressed gene, is mutated by mouse mammary tumor virus in mammary preneoplasia. PG - 1932-8 AB - 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. FAU - Marchetti, A AU - Marchetti A AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland 20892. FAU - Buttitta, F AU - Buttitta F FAU - Miyazaki, S AU - Miyazaki S FAU - Gallahan, D AU - Gallahan D FAU - Smith, G H AU - Smith GH FAU - Callahan, R AU - Callahan R LA - eng SI - GENBANK/S75221 SI - GENBANK/S75223 SI - GENBANK/S75224 PT - Journal Article PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Eukaryotic Initiation Factor-3) RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA, Messenger) RN - 0 (RNA, Neoplasm) SB - IM GS - Int-6 MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Cell Transformation, Viral MH - Cloning, Molecular MH - Eukaryotic Initiation Factor-3 MH - Gene Expression Regulation, Viral MH - Genes MH - Mammary Neoplasms, Experimental/genetics MH - Mammary Tumor Virus, Mouse/*genetics MH - Mice MH - Molecular Sequence Data MH - Mutagenesis, Insertional MH - Mutation MH - Precancerous Conditions/*genetics/microbiology MH - Proto-Oncogene Proteins/*genetics MH - Proviruses/genetics MH - RNA, Messenger/genetics MH - RNA, Neoplasm/genetics MH - Restriction Mapping MH - Sequence Homology, Nucleic Acid MH - *Virus Integration PMC - PMC188811 EDAT- 1995/03/01 00:00 MHDA- 1995/03/01 00:01 PMCR- 1995/03/01 CRDT- 1995/03/01 00:00 PHST- 1995/03/01 00:00 [pubmed] PHST- 1995/03/01 00:01 [medline] PHST- 1995/03/01 00:00 [entrez] PHST- 1995/03/01 00:00 [pmc-release] AID - 10.1128/JVI.69.3.1932-1938.1995 [doi] PST - ppublish SO - J Virol. 1995 Mar;69(3):1932-8. doi: 10.1128/JVI.69.3.1932-1938.1995.