PMID- 1372276
OWN - NLM
STAT- MEDLINE
DCOM- 19920417
LR  - 20220318
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 6
IP  - 3
DP  - 1992 Mar
TI  - Expression of an activated Notch-related int-3 transgene interferes with cell 
      differentiation and induces neoplastic transformation in mammary and salivary 
      glands.
PG  - 345-55
AB  - Expression of the int-3 locus is activated in mouse mammary tumors as a 
      consequence of insertional mutagenesis by the mouse mammary tumor virus (MMTV). 
      Integration of the MMTV provirus into the int-3 locus promotes the transcription 
      and translation of flanking cellular int-3 sequences sharing significant homology 
      with the intracellular domain of the neurogenic Notch gene of Drosophila, and 
      with the yeast cell cycle regulatory genes cdc10 and SWI6. To determine the in 
      vivo consequences of activated int-3 expression, transgenic mice were generated 
      harboring a genomic tumor DNA fragment consisting of the MMTV LTR and the 
      flanking cellular int-3 sequences. All six int-3 founder transgenic mice and the 
      progeny of one established line exhibited similar dramatic phenotypic 
      abnormalities in tissues in which the transgene was expressed. Focal and often 
      multiple poorly differentiated mammary and salivary adenocarcinomas appeared in 
      the majority of transgenic mice between 2 and 7 months of age. Significantly, 
      mammary glands were arrested in development and were lactation deficient in all 
      female int-3 mice. The salivary glands, glands of the nasal mucosa and maxillary 
      sinus, the extraorbital lacrimal glands, and the Harderian glands of juvenile and 
      adult transgenic mice all contained proliferating immature ductule cells and were 
      incompletely differentiated. In addition, all male int-3 transgenic mice were 
      sterile, apparently the result of severe hyperplasia of the epididymis. These 
      findings demonstrate in vivo that expression of the activated Notch-related int-3 
      gene causes deregulation of normal developmental controls and hyperproliferation 
      of glandular epithelia.
FAU - Jhappan, C
AU  - Jhappan C
AD  - Division of Cancer Biology, National Cancer Institute, National Institutes of 
      Health, Bethesda, Maryland 20892.
FAU - Gallahan, D
AU  - Gallahan D
FAU - Stahle, C
AU  - Stahle C
FAU - Chu, E
AU  - Chu E
FAU - Smith, G H
AU  - Smith GH
FAU - Merlino, G
AU  - Merlino G
FAU - Callahan, R
AU  - Callahan R
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 63231-63-0 (RNA)
RN  - 9007-49-2 (DNA)
SB  - IM
GS  - cdc10
GS  - int-3
GS  - sw16
MH  - Adenocarcinoma/genetics
MH  - Animals
MH  - Cell Differentiation/*genetics
MH  - Cell Transformation, Neoplastic/*genetics
MH  - DNA/genetics
MH  - Female
MH  - *Gene Expression
MH  - Hyperplasia/genetics
MH  - Male
MH  - Mammary Glands, Animal/*pathology
MH  - Mammary Neoplasms, Experimental/genetics
MH  - Mammary Tumor Virus, Mouse/*genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Plasmids
MH  - RNA/genetics
MH  - Salivary Gland Neoplasms/genetics
MH  - Salivary Glands/*pathology
EDAT- 1992/03/01 00:00
MHDA- 1992/03/01 00:01
CRDT- 1992/03/01 00:00
PHST- 1992/03/01 00:00 [pubmed]
PHST- 1992/03/01 00:01 [medline]
PHST- 1992/03/01 00:00 [entrez]
AID - 10.1101/gad.6.3.345 [doi]
PST - ppublish
SO  - Genes Dev. 1992 Mar;6(3):345-55. doi: 10.1101/gad.6.3.345.