Abstract
Connexin genes exert negative growth control when transfected into various types of tumor cell lines. We previously demonstrated that connexin 26 (Cx26) suppresses in vitro and in vivo growth of HeLa cells. In this study, we have examined whether certain Cx26 mutants can abrogate cell growth control and the gap junctional intercellular communication (GJIC) capacity of such Cx26-transfected HeLa cells. For this purpose, we transfected three mutated Cx26 genes (C60F, P87L and R143W) into HeLa cells already containing the wild-type Cx26 gene, which are GJIC-competent and non-tumorigenic. Transfection of P87L and R143W mutants enhanced the tumorigenicity of the HeLa Cx26 cells in nude mice without any change in GJIC capacity. On the other hand, transfection of the C60F mutant reduced the GJIC capacity of HeLa Cx26 cells without affecting their growth in vivo. Immunostaining studies demonstrated that the Cx26 proteins were localized mainly at cell-cell contact areas in the HeLa Cx26 cells both before and after transfection of mutated Cx26 genes. These results suggest that certain mutant Cx26 proteins exert a dominant-negative effect on Cx26-regulated growth of HeLa cells and that such effects may be independent of the effect on GJIC ability. It is proposed that wild-type and mutant Cx26 proteins produce heteromeric connexons and that such heteromeric connexons may exert different effects on growth control from those of homomeric connexons.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Duflot-Dancer, A., Mesnil, M. & Yamasaki, H. Dominant-negative abrogation of connexin-mediated cell growth control by mutant connexin genes. Oncogene 15, 2151–2158 (1997). https://doi.org/10.1038/sj.onc.1201393
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201393
Keywords
This article is cited by
-
Connexin 32 overexpression increases proliferation, reduces gap junctional intercellular communication, motility and epithelial-to-mesenchymal transition in Hs578T breast cancer cells
Journal of Cell Communication and Signaling (2022)
-
Identification of a Novel GJA8 (Cx50) Point Mutation Causes Human Dominant Congenital Cataracts
Scientific Reports (2014)
-
Implications and challenges of connexin connections to cancer
Nature Reviews Cancer (2010)
-
5-Aza-2′-deoxycytidine suppresses human renal carcinoma cell growth in a xenograft model via up-regulation of the connexin 32 gene
British Journal of Pharmacology (2008)
-
Enhancing effect of connexin 32 gene on vinorelbine-induced cytotoxicity in A549 lung adenocarcinoma cells
Cancer Chemotherapy and Pharmacology (2007)