PMID- 7884899 OWN - NLM STAT- MEDLINE DCOM- 19950410 LR - 20200724 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 69 IP - 4 DP - 1995 Apr TI - Fgf-8, activated by proviral insertion, cooperates with the Wnt-1 transgene in murine mammary tumorigenesis. PG - 2501-7 AB - We have used mouse mammary tumor virus (MMTV) infection of Wnt-1 transgenic mice to accelerate mammary tumorigenesis and to molecularly tag insertionally activated proto-oncogenes that cooperate oncogenically with Wnt-1 (G. M. Shackleford, C. A. MacArthur, H. C. Kwan, and H. E. Varmus, Proc. Natl. Acad. Sci. USA 90:740-744, 1993). Here we report the identification and characterization of a 31-kb genomic locus that contains clonal MMTV integrations in 8 of 80 mammary tumors from MMTV-infected Wnt-1 transgenic mice. Two genes were identified within this locus, one of which was transcriptionally activated by MMTV insertions. This activated gene is identical to androgen-induced growth factor (AIGF/Fgf-8) (A. Tanaka, K. Miyamoto, N. Minamino, M. Takeda, B. Sato, H. Matsuo, and K. Matsumoto, Proc. Natl. Acad. Sci. USA 89:8928-8932, 1992), the eighth member of the fibroblast growth factor (FGF) family. Transcriptional activation of Fgf-8 was found in all tumors with MMTV insertions in this locus. Fgf-8 mRNA was absent in normal mammary glands and was detected only in adult testis and ovary and in midgestational embryos. The sequences of Fgf-8 genomic and cDNA clones revealed five coding exons, in contrast to the three coding exons found in other FGF genes. cDNAs encoding three isoforms of the FGF-8 protein were isolated. The three corresponding mRNAs resulted from the alternative use of two 5' splice sites and two 3' splice sites for the second and third exons, respectively. These results implicate Fgf-8 as the third FGF gene found to cooperate with Wnt-1 in MMTV-induced murine mammary tumorigenesis, suggesting that FGFs and Wnts are strong collaborators in this process. FAU - MacArthur, C A AU - MacArthur CA AD - Department of Pediatrics, University of Southern California School of Medicine, Los Angeles. FAU - Shankar, D B AU - Shankar DB FAU - Shackleford, G M AU - Shackleford GM LA - eng SI - GENBANK/U18673 GR - CA58412/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (DNA Primers) RN - 0 (Fgf8 protein, mouse) RN - 0 (Growth Substances) RN - 0 (Neoplasm Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Wnt Proteins) RN - 0 (Wnt1 Protein) RN - 0 (Wnt1 protein, mouse) RN - 0 (Zebrafish Proteins) RN - 148997-75-5 (Fibroblast Growth Factor 8) RN - 62031-54-3 (Fibroblast Growth Factors) SB - IM GS - Fgf-8 GS - Wnt-1 MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Cloning, Molecular MH - DNA Primers MH - Exons MH - Female MH - Fibroblast Growth Factor 8 MH - *Fibroblast Growth Factors MH - Growth Substances/*genetics MH - Mammary Neoplasms, Experimental/*genetics/virology MH - Mammary Tumor Virus, Mouse/genetics MH - Mice MH - Mice, Transgenic MH - Molecular Sequence Data MH - Neoplasm Proteins/*genetics MH - Proto-Oncogene Proteins/*genetics MH - Proviruses/*genetics MH - RNA Splicing MH - Virus Integration MH - Wnt Proteins MH - Wnt1 Protein MH - *Zebrafish Proteins PMC - PMC188926 EDAT- 1995/04/01 00:00 MHDA- 1995/04/01 00:01 PMCR- 1995/04/01 CRDT- 1995/04/01 00:00 PHST- 1995/04/01 00:00 [pubmed] PHST- 1995/04/01 00:01 [medline] PHST- 1995/04/01 00:00 [entrez] PHST- 1995/04/01 00:00 [pmc-release] AID - 10.1128/JVI.69.4.2501-2507.1995 [doi] PST - ppublish SO - J Virol. 1995 Apr;69(4):2501-7. doi: 10.1128/JVI.69.4.2501-2507.1995.