PMID- 9285723
OWN - NLM
STAT- MEDLINE
DCOM- 19980203
LR  - 20231213
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 7
IP  - 9
DP  - 1997 Sep 1
TI  - High incidence of spontaneous and chemically induced liver tumors in mice 
      deficient for connexin32.
PG  - 713-6
AB  - Connexins are subunits of gap junction channels, which mediate the direct 
      transfer of ions, second messenger molecules and other metabolites between 
      contacting cells. Gap junctions are thought to be involved in tissue homeostasis, 
      embryonic development and the control of cell proliferation [1,2]. It has also 
      been suggested that the loss of intercellular communication via gap junctions may 
      contribute to multistage carcinogenesis [3-5]. We have previously shown that 
      transgenic mice that lack connexin32 (Cx32), the major gap junction protein 
      expressed in hepatocytes, express lower levels of a second hepatic gap junction 
      protein, Cx26, suggesting that Cx32 has a stabilizing effect on Cx26 [6]. Here, 
      we report that male and female one-year-old mice deficient for Cx32 had 25-fold 
      more and 8-fold more spontaneous liver tumors than wild-type mice, respectively. 
      Incorporation of bromodeoxyuridine (BrdU) into the liver was higher for 
      Cx32-deficient mice than for wild-type mice, suggesting that their hepatocyte 
      proliferation rate was higher. Furthermore, intraperitoneal injection, two weeks 
      after birth, of the carcinogen diethylnitrosamine (DEN) led, after one year, both 
      to more liver tumors in Cx32-deficient mice than in controls, and to accelerated 
      tumor growth. Loss of Cx32 protein from hepatic gap junctions is therefore likely 
      to cause enhanced clonal survival and expansion of mutated ('initiated') cells, 
      which results in a higher susceptibility to hepatic tumors. Our results 
      demonstrate that functional gap junctions inhibit the development of spontaneous 
      and chemically induced tumors in mouse liver.
FAU - Temme, A
AU  - Temme A
AD  - Institut fur Genetik, Abt. Molekulargenetik, Universitat Bonn, Romerstr. 164, 
      53117 Bonn, Germany.
FAU - Buchmann, A
AU  - Buchmann A
FAU - Gabriel, H D
AU  - Gabriel HD
FAU - Nelles, E
AU  - Nelles E
FAU - Schwarz, M
AU  - Schwarz M
FAU - Willecke, K
AU  - Willecke K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Carcinogens)
RN  - 0 (Connexins)
RN  - 3IQ78TTX1A (Diethylnitrosamine)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - Animals
MH  - Blotting, Northern
MH  - Bromodeoxyuridine/metabolism
MH  - Carcinogens/pharmacology
MH  - Connexins/deficiency/*physiology
MH  - Diethylnitrosamine/pharmacology
MH  - Female
MH  - Fluorescent Antibody Technique, Indirect
MH  - Incidence
MH  - Liver Neoplasms, Experimental/chemically induced/*etiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Gap Junction beta-1 Protein
EDAT- 1997/09/01 00:00
MHDA- 1997/09/01 00:01
CRDT- 1997/09/01 00:00
PHST- 1997/09/01 00:00 [pubmed]
PHST- 1997/09/01 00:01 [medline]
PHST- 1997/09/01 00:00 [entrez]
AID - S0960-9822(06)00302-2 [pii]
AID - 10.1016/s0960-9822(06)00302-2 [doi]
PST - ppublish
SO  - Curr Biol. 1997 Sep 1;7(9):713-6. doi: 10.1016/s0960-9822(06)00302-2.