PMID- 9506519
OWN - NLM
STAT- MEDLINE
DCOM- 19980330
LR  - 20220224
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 92
IP  - 5
DP  - 1998 Mar 6
TI  - Intestinal tumorigenesis in compound mutant mice of both Dpc4 (Smad4) and Apc 
      genes.
PG  - 645-56
AB  - The DPC4 (SMAD4) gene plays a key role in the TGFbeta signaling pathway. We 
      inactivated its mouse homolog Dpc4 (Smad4). The homozygous mutants were embryonic 
      lethal, whereas the heterozygotes showed no abnormality. We then introduced the 
      Dpc4 mutation into the Apc(delta716) knockout mice, a model for human familial 
      adenomatous polyposis. Because both Apc and Dpc4 are located on chromosome 18, we 
      constructed compound heterozygotes carrying both mutations on the same chromosome 
      by meiotic recombination. In such mice, intestinal polyps developed into more 
      malignant tumors than those in the simple Apc(delta716) heterozygotes, showing an 
      extensive stromal cell proliferation, submucosal invasion, cell type 
      heterogeneity, and in vivo transplantability. These results indicate that 
      mutations in DPC4 (SMAD4) play a significant role in the malignant progression of 
      colorectal tumors.
FAU - Takaku, K
AU  - Takaku K
AD  - Banyu Tsukuba Research Institute (Merck), Japan.
FAU - Oshima, M
AU  - Oshima M
FAU - Miyoshi, H
AU  - Miyoshi H
FAU - Matsui, M
AU  - Matsui M
FAU - Seldin, M F
AU  - Seldin MF
FAU - Taketo, M M
AU  - Taketo MM
LA  - eng
GR  - HG00734/HG/NHGRI NIH HHS/United States
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  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (SMAD4 protein, human)
RN  - 0 (Smad4 Protein)
RN  - 0 (Smad4 protein, mouse)
RN  - 0 (Trans-Activators)
SB  - IM
CIN - Cell. 1998 Mar 6;92(5):591-2. PMID: 9506511
MH  - Adenocarcinoma/chemistry/*genetics/pathology
MH  - Adenomatous Polyposis Coli/*genetics/pathology
MH  - Animals
MH  - Chromosome Deletion
MH  - Colonic Neoplasms/chemistry/*genetics/pathology
MH  - Crosses, Genetic
MH  - *DNA-Binding Proteins
MH  - Disease Progression
MH  - Duodenal Neoplasms/chemistry/pathology
MH  - Genes, APC/*physiology
MH  - Genes, Tumor Suppressor/*physiology
MH  - Heterozygote
MH  - Homozygote
MH  - Humans
MH  - Intestinal Polyps/chemistry/genetics/pathology
MH  - Intestine, Small
MH  - Loss of Heterozygosity
MH  - Mice
MH  - Mice, Knockout
MH  - Neoplasm Invasiveness
MH  - Smad4 Protein
MH  - Trans-Activators/analysis/*genetics
MH  - Tumor Cells, Cultured
EDAT- 1998/03/20 00:00
MHDA- 1998/03/20 00:01
CRDT- 1998/03/20 00:00
PHST- 1998/03/20 00:00 [pubmed]
PHST- 1998/03/20 00:01 [medline]
PHST- 1998/03/20 00:00 [entrez]
AID - S0092-8674(00)81132-0 [pii]
AID - 10.1016/s0092-8674(00)81132-0 [doi]
PST - ppublish
SO  - Cell. 1998 Mar 6;92(5):645-56. doi: 10.1016/s0092-8674(00)81132-0.