Journal Article

Unexpected role for the human Cx37 C1019T polymorphism in tumour cell proliferation

Sandrine Morel, Laurent Burnier, Angela Roatti, Alexandra Chassot, Isabelle Roth, Esther Sutter, Katia Galan, Anna Pfenniger, Marc Chanson and Brenda R. Kwak

in Carcinogenesis

Volume 31, issue 11, pages 1922-1931
Published in print November 2010 | ISSN: 0143-3334
Published online August 2010 | e-ISSN: 1460-2180 | DOI:
Unexpected role for the human Cx37 C1019T polymorphism in tumour cell proliferation

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics


Show Summary Details


Connexins are a large family of proteins that form gap junction channels allowing exchange of ions and small metabolites between neighboring cells. They have been implicated in pathological processes such as tumourigenesis in which they may act as tumour suppressors. A polymorphism in the human connexin37 (Cx37) gene (C1019T), resulting in a non-conservative amino acid change in the regulatory C-terminus (CT) of the Cx37 protein (P319S) has been suggested to be implicated in predisposition to angiosarcomas. In this study, we have used communication-deficient HeLa and SK-HEP-1 cells transfected with Cx37-319S, Cx37-319P or empty vector. We showed that the expression of Cx37-319P limited proliferation of HeLa and SK-HEP-1 cells, whereas Cx37-319S expression was without effect. Using an in vitro kinase assay, we demonstrated phosphorylation of Cx37 CT by glycogen synthase kinase-3 (GSK-3), a kinase known to be implicated in cell proliferation and cancer. GSK-3-induced phosphorylation was associated with reduced gap junctional intercellular communication (GJIC) as measured by microinjection of the tracer neurobiotin. Inhibition of GSK-3 by LiCl or SB415286 reduced phosphorylation of Cx37-319P and increased GJIC. This latter effect on GJIC involved the beta and not the alpha isoform of GSK-3. In contrast, GSK-3 inhibitors were without effect on HeLa cells expressing Cx37-319S. In conclusion, our data indicate functional effects of the Cx37 C1019T polymorphism on GJIC that might contribute to tumour cell growth.

Journal Article.  7262 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.