PMID- 8380647
OWN - NLM
STAT- MEDLINE
DCOM- 19930218
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 90
IP  - 2
DP  - 1993 Jan 15
TI  - Mouse mammary tumor virus infection accelerates mammary carcinogenesis in Wnt-1 
      transgenic mice by insertional activation of int-2/Fgf-3 and hst/Fgf-4.
PG  - 740-4
AB  - Transgenic mice carrying the Wnt-1 protooncogene modified for expression in 
      mammary epithelial cells exhibit hyperplastic mammary glands and stochastically 
      develop mammary carcinomas, suggesting that additional events are necessary for 
      tumorigenesis. To induce such events and to identify the genes involved, we have 
      infected Wnt-1 transgenic mice with mouse mammary tumor virus (MMTV), intending 
      to insertionally activate, and thereby molecularly tag, cooperating 
      protooncogenes. Infection of breeding female Wnt-1 transgenics decreased the 
      average age at which tumors appeared from approximately 4 months to approximately 
      2.5 months and increased the average number of primary tumors per mouse from 1-2 
      to > 5. A smaller effect was observed in virgin females, and infection of 
      transgenic males showed no significant effect on tumor latency. More than half of 
      the tumors from the infected breeding group contained one or more newly acquired 
      MMTV proviruses in a pattern suggesting that most cells in tumors arose from a 
      single infected cell. Analyses of provirus-containing tumors for induced or 
      altered expression of int-2/Fgf-3, hst/Fgf-4, int-3, and Wnt-3 showed activation 
      of int-2 in 39% of tumors, hst in 3%, and both int-2 and hst in 3%. DNA analyses 
      with probes for protooncogenes and MMTV confirmed that the activations resulted 
      from proviral insertions. There was no evidence for proviral insertions at the 
      int-3, Wnt-3, or Wnt-1 loci. These findings provide further evidence that 
      fibroblast growth factors Int-2 and Hst can cooperate with Wnt-1, another 
      secreted factor, in mammary tumorigenesis, and they illustrate the capacity of 
      this system to identify cooperating oncogenes.
FAU - Shackleford, G M
AU  - Shackleford GM
AD  - Division of Hematology-Oncology, Childrens Hospital Los Angeles, CA.
FAU - MacArthur, C A
AU  - MacArthur CA
FAU - Kwan, H C
AU  - Kwan HC
FAU - Varmus, H E
AU  - Varmus HE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Fgf3 protein, mouse)
RN  - 0 (Fgf4 protein, mouse)
RN  - 0 (Fibroblast Growth Factor 3)
RN  - 0 (Fibroblast Growth Factor 4)
RN  - 0 (Proto-Oncogene Proteins)
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  - Fgf-4
GS  - Wnt-1
GS  - hst
GS  - int-2
GS  - int-3
MH  - Animals
MH  - Cell Transformation, Neoplastic/*genetics
MH  - Female
MH  - Fibroblast Growth Factor 3
MH  - Fibroblast Growth Factor 4
MH  - Fibroblast Growth Factors/genetics
MH  - *Gene Expression Regulation, Neoplastic
MH  - Male
MH  - Mammary Neoplasms, Experimental/genetics/*microbiology
MH  - Mammary Tumor Virus, Mouse/*pathogenicity
MH  - Mice
MH  - Mice, Transgenic
MH  - Mutagenesis, Insertional/*genetics
MH  - Proto-Oncogene Proteins/*genetics
MH  - Proto-Oncogenes/genetics
MH  - Proviruses/isolation & purification
MH  - Time Factors
MH  - Transcription, Genetic
MH  - Virus Integration/genetics
MH  - Wnt Proteins
MH  - Wnt1 Protein
MH  - *Zebrafish Proteins
PMC - PMC45741
EDAT- 1993/01/15 00:00
MHDA- 1993/01/15 00:01
PMCR- 1993/07/15
CRDT- 1993/01/15 00:00
PHST- 1993/01/15 00:00 [pubmed]
PHST- 1993/01/15 00:01 [medline]
PHST- 1993/01/15 00:00 [entrez]
PHST- 1993/07/15 00:00 [pmc-release]
AID - 10.1073/pnas.90.2.740 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):740-4. doi: 10.1073/pnas.90.2.740.