Carcinogenesis, Vol. 20, No. 10, 1913-1918,
October 1999
© 1999 Oxford University Press
Cancer Biology |
Gap junction proteins connexin32 and connexin43 partially acquire growth-suppressive function in HeLa cells by deletion of their C-terminal tails
Unit of Multistage Carcinogenesis, International Agency for Research on Cancer, 150 cours Albert-Thomas, 69372 Lyon Cedex 08, France
Our laboratory has previously reported that transfection of a connexin26 (Cx26) gene, but not connexin40 nor connexin43 (Cx43), into HeLa cells expressing no detectable level of connexins suppressed the tumorigenic phenotype of the HeLa cells both in vitro and in vivo, although all of these connexins induced gap junctional intercellular communication in HeLa cells to a similar extent. The most remarkable structural difference between connexin proteins is the length of the C-terminal cytoplasmic tail, Cx26 having almost no tail, while Cx43 and connexin32 (Cx32) have long and intermediate ones, respectively. When Cx32 and Cx43 lose their C-terminal tails, they seem to resemble Cx26 in structure. To examine whether such truncated connexins become tumor suppressive in HeLa cells, we introduced a stop codon into each of the Cx32 and Cx43 cDNAs to remove their C-terminal tails and transfected these constructs (
Cx) into HeLa cells. Both Cx cDNAs induced GJIC as efficiently as the wild-type counterparts. Although none of the truncated connexins affected proliferation rate, the truncated Cx32 and Cx43 proteins suppressed anchorage-independent cell growth in soft agar. Furthermore, when the transfectants were injected into the backs of nude mice, tumor appearance was delayed by 7 days in animals given cells expressing truncated connexins, i.e. tumors became detectable on days 11 and 18 after injection of vector and Cx transfectants, respectively. Although throughout these experiments the truncated connexins did not completely eliminate the tumorigenicity of HeLa cells, as Cx26 did, it was evident that deletion of the C-terminal tails gave both Cx32 and Cx43 a capacity for negative growth control, suggesting that the C-terminal tails of these two connexins function as a regulatory region for connexin-mediated growth control in HeLa cells.
Abbreviations: Cx26, connexin26; Cx32, connexin32; Cx43, connexin43; FCS, fetal calf serum; GJIC, gap junctional intercellular communication; LPA, lysophosphatidic acid.
1 To whom correspondence should be addressed Email: yamasaki{at}iarc.fr
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Y. Rhee, X.-Q. Zhao, R. J. B. Francis, G. Y. Huang, J. D. Mably, and C. W. Lo Connexin 43 regulates epicardial cell polarity and migration in coronary vascular development Development, September 15, 2009; 136(18): 3185 - 3193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. OZAWA, H. MUTAI, T. MATSUNAGA, Y. TOKUMARU, M. FUJII, K. SAKAMOTO, T. TOMITA, and K. OGAWA Promoted Cell Proliferation by Connexin 30 Gene Transfection to Head-and-Neck Cancer Cell Line Anticancer Res, June 1, 2009; 29(6): 1981 - 1985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. De Vuyst, E. Decrock, M. De Bock, H. Yamasaki, C. C. Naus, W. H. Evans, and L. Leybaert Connexin Hemichannels and Gap Junction Channels Are Differentially Influenced by Lipopolysaccharide and Basic Fibroblast Growth Factor Mol. Biol. Cell, January 1, 2007; 18(1): 34 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. N.G Giepmans Gap junctions and connexin-interacting proteins Cardiovasc Res, May 1, 2004; 62(2): 233 - 245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Chipman, A. Mally, and G. O. Edwards Disruption of Gap Junctions in Toxicity and Carcinogenicity Toxicol. Sci., February 1, 2003; 71(2): 146 - 153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Muramatsu, M. Iwai, T. Morikawa, S. Tanaka, T. Mori, Y. Harada, and T. Okanoue Influence of transfection with connexin 26 gene on malignant potential of human hepatoma cells Carcinogenesis, February 1, 2002; 23(2): 351 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yano, F.-J. Hernandez-Blazquez, Y. Omori, and H. Yamasaki Reduction of malignant phenotype of HEPG2 cell is associated with the expression of connexin 26 but not connexin 32 Carcinogenesis, October 1, 2001; 22(10): 1593 - 1600. [Abstract] [Full Text] [PDF]
|
|