Connexin over-expression differentially suppresses glioma growth and contributes to the bystander effect following HSV-thymidine kinase gene therapy.

Abstract

Neoplastic transformation is frequently associated with a loss of gap junctional intercellular communication and reduced expression of connexins. The introduction of connexin genes into tumor cells reverses the proliferative characteristics of such cells. However, there is very little comparative information on the effects of different connexins on cancer cell growth. We hypothesized that Cx26, Cx32, or Cx43 would display differential growth suppression of C6 glioma cells and uniquely modulate the bystander effect following transduction of C6 cells with HSVtk followed by suicide gene therapy. The bystander phenomenon is the death of a greater number of tumor cells than are expressing the HSVtk gene, presumably due to the passage of toxic molecules through gap junction channels. To test this hypothesis, we used retroviral vectors to infect C6 glioma cells producing connexin-expressing and HSVtk-expressing cell lines. All three connexin-expressing cell lines grew significantly slower than GFP-infected or native C6 cells. Cx32 and Cx26 were significantly more effective at mediating the bystander effect in cocultures of C6-connexin cells with C6-HSVtk cells. These studies indicate that connexins have unique properties that contribute to their tumor suppressive function.

• Authors: Tomas Jimenez, W Paul Fox, Christian C G Naus, Jacques Galipeau, Daniel J Belliveau
• Journal: Cell communication & adhesion (Cell Commun Adhes) 2006 Jan-Apr Vol. 13 Issue 1-2 Pg. 79-92 ISSN: 1541-9061 [Print] England
• PMID: 16613782 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Connexin 43
• Connexins
• GJB2 protein, human
• Prodrugs
• connexin 32
• Connexin 26
• Thymidine Kinase
• Ganciclovir

Topics

• Bystander Effect (physiology)
• Cell Survival
• Coculture Techniques
• Connexin 26
• Connexin 43 (metabolism)
• Connexins (metabolism)
• Ganciclovir (pharmacology)
• Gap Junctions (drug effects, metabolism)
• Genes, Transgenic, Suicide
• Genetic Therapy
• Glioma (metabolism, pathology, therapy)
• Herpesvirus 1, Human (enzymology, genetics)
• Humans
• Prodrugs (pharmacology)
• Thymidine Kinase (genetics)
• Tumor Cells, Cultured (drug effects, metabolism)