PMID- 9811675 OWN - NLM STAT- MEDLINE DCOM- 19981130 LR - 20200724 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 72 IP - 12 DP - 1998 Dec TI - Mouse mammary tumor virus sequences responsible for activating cellular oncogenes. PG - 9428-35 AB - Integration of mouse mammary tumor virus (MMTV) near the int genes results in the inappropriate expression of these proto-oncogenes and initiates events that lead to the formation of mammary adenocarcinomas. In most cases, the MMTV provirus integrates in a transcriptional orientation opposite that of the int genes. We have used a novel, vector-based system designed to recapitulate the integration of MMTV upstream of the int-2 promoter. Compared to a cellular promoter or another retroviral promoter, the MMTV long terminal repeat (LTR) in this configuration is particularly efficacious at activating the int-2 promoter. The sequences responsible for enhancing the activity of the int-2 promoter map to two domains in the 5' end of the MMTV LTR. One domain is a previously defined element; the second is an element delineated by these studies that acts synergistically with the first. Both of these elements display mammary cell-specific activity. Thus, even though the MMTV promoter itself is weak without hormonal stimulation, viral integration can position the 5' LTR elements to efficiently activate transcription from cellular proto-oncogenes. Other functional elements in the LTR have little effect on the activation of the int-2 promoter. Even stimulation of the MMTV promoter with steroid hormones only modestly activates transcription from the int-2 promoter, suggesting that the 5' elements of the LTR are the predominant determinants of the tissue- and orientation-specific activation of cellular promoters by MMTV. FAU - Grimm, S L AU - Grimm SL AD - Program in Molecular Biology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. FAU - Nordeen, S K AU - Nordeen SK LA - eng GR - R01 DK037061/DK/NIDDK NIH HHS/United States GR - DK-37061/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (FGF3 protein, human) RN - 0 (Fgf3 protein, mouse) RN - 0 (Fibroblast Growth Factor 3) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Steroids) RN - 62031-54-3 (Fibroblast Growth Factors) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - Base Sequence MH - Cell Line MH - DNA/genetics MH - Enhancer Elements, Genetic MH - Female MH - Fibroblast Growth Factor 3 MH - Fibroblast Growth Factors/genetics MH - Gene Expression Regulation MH - Genetic Vectors MH - HeLa Cells MH - Humans MH - Mammary Neoplasms, Experimental/etiology/genetics/virology MH - Mammary Tumor Virus, Mouse/drug effects/*genetics/*pathogenicity MH - Mice MH - Promoter Regions, Genetic/drug effects MH - Proto-Oncogene Proteins/genetics MH - *Proto-Oncogenes/drug effects MH - Proviruses/genetics MH - Retroviridae Infections/etiology/genetics/virology MH - Steroids/pharmacology MH - Terminal Repeat Sequences MH - Transfection MH - Tumor Virus Infections/etiology/genetics/virology MH - Virus Integration/genetics PMC - PMC110428 EDAT- 1998/11/13 00:00 MHDA- 1998/11/13 00:01 PMCR- 1998/12/01 CRDT- 1998/11/13 00:00 PHST- 1998/11/13 00:00 [pubmed] PHST- 1998/11/13 00:01 [medline] PHST- 1998/11/13 00:00 [entrez] PHST- 1998/12/01 00:00 [pmc-release] AID - 0813 [pii] AID - 10.1128/JVI.72.12.9428-9435.1998 [doi] PST - ppublish SO - J Virol. 1998 Dec;72(12):9428-35. doi: 10.1128/JVI.72.12.9428-9435.1998.