PMID- 8386870 OWN - NLM STAT- MEDLINE DCOM- 19930527 LR - 20081121 IS - 0042-6822 (Print) IS - 0042-6822 (Linking) VI - 194 IP - 1 DP - 1993 May TI - Activation of both Wnt-1 and Fgf-3 by insertion of mouse mammary tumor virus downstream in the reverse orientation: a reappraisal of the enhancer insertion model. PG - 157-65 AB - In retrovirus-induced tumors, proviral DNA is commonly found next to or within a cellular proto-oncogene such that transcription of the gene is influenced by the viral promoter or enhancer. Extensive surveys of naturally occurring tumors reveal that proviruses integrated on the 3' side of the gene are usually in the same transcriptional orientation, suggesting a model in which the bidirectional viral enhancer acts primarily on the closest promoters. Here we describe a virally induced mammary tumor that appears to contradict these ideas since the Wnt-1/int-1 and Fgf-3/int-2 proto-oncogenes have both been activated by mouse mammary tumor virus (MMTV) DNA integrated 3' of the gene in the opposite transcriptional orientation. However, by cloning the relevant DNAs, we show that these are not simple proviral insertions. In the Wnt-1 locus, there is an additional LTR immediately adjacent to the 3' end of the MMTV provirus, while in Fgf-3, the provirus has sustained a deletion that removes the 5' LTR, gag, and most of pol. These structural alterations can be reconciled with the enhancer insertion model by postulating that the viral enhancer can only function if it is not transcribed. FAU - Clausse, N AU - Clausse N AD - Imperial Cancer Research Fund Laboratories, London, United Kingdom. FAU - Baines, D AU - Baines D FAU - Moore, R AU - Moore R FAU - Brookes, S AU - Brookes S FAU - Dickson, C AU - Dickson C FAU - Peters, G AU - Peters G LA - eng SI - GENBANK/X68450 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Virology JT - Virology JID - 0110674 RN - 0 (DNA, Viral) RN - 0 (Fgf3 protein, mouse) RN - 0 (Fibroblast Growth Factor 3) RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA, Messenger) RN - 0 (RNA, Viral) RN - 0 (Wnt Proteins) RN - 0 (Wnt1 Protein) RN - 0 (Wnt1 protein, mouse) RN - 0 (Zebrafish Proteins) RN - 0 (fgf3 protein, zebrafish) RN - 62031-54-3 (Fibroblast Growth Factors) SB - IM GS - Fgf-3 GS - Wnt-1 MH - Animals MH - Base Sequence MH - Cloning, Molecular MH - DNA, Viral/analysis/genetics MH - Enhancer Elements, Genetic/*genetics MH - Evaluation Studies as Topic MH - Fibroblast Growth Factor 3 MH - *Fibroblast Growth Factors MH - Genes, gag/genetics MH - Genes, pol/genetics MH - Genome, Viral MH - Mammary Tumor Virus, Mouse/*genetics MH - Mice MH - Models, Genetic MH - Molecular Sequence Data MH - Mutagenesis, Insertional MH - Proto-Oncogene Proteins/*genetics MH - Proviruses/*genetics MH - RNA, Messenger/genetics MH - RNA, Viral/analysis MH - Repetitive Sequences, Nucleic Acid/genetics MH - Sequence Analysis, DNA MH - *Transcription, Genetic MH - Virus Integration/genetics MH - Wnt Proteins MH - Wnt1 Protein MH - *Zebrafish Proteins EDAT- 1993/05/01 00:00 MHDA- 1993/05/01 00:01 CRDT- 1993/05/01 00:00 PHST- 1993/05/01 00:00 [pubmed] PHST- 1993/05/01 00:01 [medline] PHST- 1993/05/01 00:00 [entrez] AID - S0042-6822(83)71245-6 [pii] AID - 10.1006/viro.1993.1245 [doi] PST - ppublish SO - Virology. 1993 May;194(1):157-65. doi: 10.1006/viro.1993.1245.