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

Cell Communication & Adhesion
Tomas JimenezDaniel J Belliveau

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 contribu...Continue Reading

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Citations

Mar 31, 2009·Clinical & Experimental Metastasis·Khair ElzarradAbu-Bakr Al-Mehdi
Mar 5, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Bakhos A TannousXandra O Breakefield
Feb 20, 2007·Molecular Aspects of Medicine·Daniel PortsmouthMatthias Renner
Jun 7, 2014·Frontiers in Physiology·Zahra MoinfarPedro M Faustmann
Dec 7, 2007·Molecular Carcinogenesis·Grégory MennecierMarc Mesnil
Mar 26, 2010·Cell and Tissue Research·Melissa MorleyDaniel J Belliveau
Jul 31, 2019·Cellular and Molecular Life Sciences : CMLS·Fengming LiuXuebin Qin
Mar 11, 2011·Molecular Cancer Therapeutics·Laura Garcia-RodríguezCristina Fillat
Jan 14, 2022·Oncogenesis·Kevin J PridhamZhi Sheng

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