PMID- 9869455
OWN - NLM
STAT- MEDLINE
DCOM- 19990106
LR  - 20151119
IS  - 0899-1987 (Print)
IS  - 0899-1987 (Linking)
VI  - 23
IP  - 4
DP  - 1998 Dec
TI  - Inhibition of intrinsic gap-junction intercellular communication and enhancement 
      of tumorigenicity of the rat bladder carcinoma cell line BC31 by a 
      dominant-negative connexin 43 mutant.
PG  - 254-61
AB  - The tumor-suppressive property of the connexin gap-junction proteins was 
      postulated from the fact that their function of cell coupling is impaired in most 
      cancer cells. However, in conflict with this notion, certain cancer cells are 
      able to communicate through gap junctions despite their malignancy. To explain 
      this phenomenon, we studied by using a dominant-negative strategy the effect on 
      tumorigenicity of loss of intrinsic gap-junction intercellular communication 
      (GJIC) in the rat bladder carcinoma cell line BC31, which shows both expression 
      of connexin 43 (Cx43) and intercellular communication. In cells transfected with 
      a mutant Cx43 with seven residues deleted from the internal loop at positions 
      130-136 (Cx43delta), transport of the resulting connexin protein to the plasma 
      membrane occurred normally, but the GJIC of the cells was effectively abolished 
      at the level of permeability of established gap junctions. Dominant-negative 
      inhibition of GJIC by Cx43delta accelerated growth of BC31 cells in nude mice. In 
      contrast, when GJIC in BC31 cells was artificially enforced by transfection of 
      wild-type Cx43, the cells lost the capacity to grow in vivo. Decreased 
      phosphorylation of Cx43delta suggested close interaction of the internal loop of 
      connexin with its commonly phosphorylated domains in the C-terminal tail and 
      involvement of this interaction in gap-junction permeability. Therefore, we 
      conclude that the intrinsic GJIC observed in cancer cells should be considered a 
      tumor-suppressor factor and that its level may influence malignant growth 
      capacity.
FAU - Krutovskikh, V A
AU  - Krutovskikh VA
AD  - International Agency for Research on Cancer, Lyon, France.
FAU - Yamasaki, H
AU  - Yamasaki H
FAU - Tsuda, H
AU  - Tsuda H
FAU - Asamoto, M
AU  - Asamoto M
LA  - eng
GR  - 2R01 CA 40534-10A2/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.
PL  - United States
TA  - Mol Carcinog
JT  - Molecular carcinogenesis
JID - 8811105
RN  - 0 (Coloring Agents)
RN  - 0 (Connexin 43)
RN  - 0 (Isoquinolines)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 9654F8OVKE (lucifer yellow)
SB  - IM
MH  - Animals
MH  - Carcinoma, Transitional Cell/*genetics/pathology
MH  - Cell Communication/*genetics
MH  - Coloring Agents/metabolism
MH  - Connexin 43/chemistry/*genetics/physiology
MH  - Gap Junctions/*physiology
MH  - Genes, Dominant
MH  - Isoquinolines/metabolism
MH  - Mice
MH  - Mice, Nude
MH  - Mutagenesis, Site-Directed
MH  - Neoplasm Proteins/chemistry/*genetics/physiology
MH  - Neoplasm Transplantation
MH  - Protein Conformation
MH  - Rats
MH  - Recombinant Fusion Proteins/physiology
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Urinary Bladder Neoplasms/*genetics/pathology
EDAT- 1998/12/30 03:03
MHDA- 2000/06/20 09:00
CRDT- 1998/12/30 03:03
PHST- 1998/12/30 03:03 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1998/12/30 03:03 [entrez]
AID - 10.1002/(SICI)1098-2744(199812)23:4<254::AID-MC9>3.0.CO;2-4 [pii]
PST - ppublish
SO  - Mol Carcinog. 1998 Dec;23(4):254-61.