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

Tomas Jimenez, W. Paul Fox, Christian C.G. Naus, Jacques Galipeau, Daniel J. Belliveau

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

29 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)79-92
Número de páginas14
PublicaciónCell Communication and Adhesion
Volumen13
N.º1-2
DOI
EstadoPublished - ene. 2006
Publicado de forma externa

Nota bibliográfica

Funding Information:
This work was supported by a grant from the Cancer Research Society to DJB and CCGN. TJ was supported by an Ontario Graduate Scholarship in Science and Technology and the Brain Tumour Foundation. Roche Pharmaceuticals generously provided the ganciclovir used in these studies.

ASJC Scopus Subject Areas

  • Clinical Biochemistry
  • Cell Biology

PubMed: MeSH publication types

  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't

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