PMID- 14688024
OWN - NLM
STAT- MEDLINE
DCOM- 20040714
LR  - 20231213
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 25
IP  - 4
DP  - 2004 Apr
TI  - Delayed liver regeneration and increased susceptibility to chemical 
      hepatocarcinogenesis in transgenic mice expressing a dominant-negative mutant of 
      connexin32 only in the liver.
PG  - 483-92
AB  - A growing body of evidence from in vitro studies indicates that gap junction 
      proteins connexins may have a tumor-suppressor function. Our previous double 
      transfection experiments on HeLa cells have shown that a dominant-negative mutant 
      V139 M of connexin32 (Cx32) can abolish gap junctional intercellular 
      communication (GJIC). To examine whether the same dominant-negative mutant of 
      Cx32 inhibits GJIC between hepatocytes in vivo and thus modulates cell 
      proliferation and susceptibility to hepatocarcinogenesis, we created transgenic 
      mice with the mutant Cx32 gene driven by a liver-specific albumin promoter. These 
      mice developed normally both before and after birth, and GJIC in their liver was 
      diminished, as expected. No increase in incidence of spontaneous tumors of any 
      site was observed in the transgenic mice. Rather unexpectedly, cell proliferation 
      during liver regeneration after partial hepatectomy was retarded by 24 h in the 
      transgenic mice compared with the wild-type mice. In contrast, the transgenic 
      male mice were more susceptible to diethylnitrosamine-induced 
      hepatocarcinogenesis, developing more liver tumors with shorter latency. These 
      results show that GJIC can coordinate cell growth both positively and negatively 
      in vivo, supporting the idea that GJIC is essential for maintenance of 
      homeostasis.
FAU - Dagli, Maria Lucia Zaidan
AU  - Dagli ML
AD  - Unit of Multistage Carcinogenesis, International Agency for Research on Cancer, 
      150, cours Albert-Thomas, 69372 Lyon Cedex 08, France.
FAU - Yamasaki, Hiroshi
AU  - Yamasaki H
FAU - Krutovskikh, Vladimir
AU  - Krutovskikh V
FAU - Omori, Yasufumi
AU  - Omori Y
LA  - eng
GR  - R01-CA40534/CA/NCI 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.
DEP - 20031219
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Connexins)
RN  - 0 (Serum Albumin)
RN  - 3IQ78TTX1A (Diethylnitrosamine)
SB  - IM
MH  - Amino Acid Substitution
MH  - Animals
MH  - Base Sequence
MH  - Carcinoma, Hepatocellular/chemically induced/*genetics
MH  - Connexins/*genetics
MH  - Diethylnitrosamine/*toxicity
MH  - Disease Susceptibility
MH  - Genotype
MH  - HeLa Cells
MH  - Humans
MH  - Liver/pathology/*physiology
MH  - Liver Neoplasms/chemically induced/*genetics
MH  - Liver Regeneration/*genetics
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Mutagenesis, Site-Directed
MH  - Polymerase Chain Reaction
MH  - Promoter Regions, Genetic
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Serum Albumin/genetics
MH  - Gap Junction beta-1 Protein
EDAT- 2003/12/23 05:00
MHDA- 2004/07/15 05:00
CRDT- 2003/12/23 05:00
PHST- 2003/12/23 05:00 [pubmed]
PHST- 2004/07/15 05:00 [medline]
PHST- 2003/12/23 05:00 [entrez]
AID - bgh050 [pii]
AID - 10.1093/carcin/bgh050 [doi]
PST - ppublish
SO  - Carcinogenesis. 2004 Apr;25(4):483-92. doi: 10.1093/carcin/bgh050. Epub 2003 Dec 
      19.