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[Cancer Research 62, 3544-3548, June 15, 2002]
© 2002 American Association for Cancer Research


Tumor Biology

Ciliary Neurotrophic Factor (CNTF) in Combination with Its Soluble Receptor (CNTFR{alpha}) Increases Connexin43 Expression and Suppresses Growth of C6 Glioma Cells1

Mark A. Ozog, John F. Bechberger and Christian C. G. Naus2

Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario N6A 5C1, Canada

The loss of gap junctional intercellular communication has been proposedas playing a major role in the process of carcinogenesis. Most neoplastic cells, including C6 gliomas, express less connexins and have fewer gap junctions, reduced gap junctional intercellular communication, and increased growth rates compared with their nonneoplastic counterparts. The purpose of this study was to determine whether ciliary neurotrophic factor (CNTF) can be used to increase endogenous connexin43 levels, increase intercellular coupling, and retard the growth rate of C6 glioma cells. C6 cells were grown in serum-reduced medium (1% serum) and exposed to the following agents: vehicle (PBS), CNTF (20 ng/ml), CNTF soluble receptor (CNTFR{alpha}; 200 ng/ml), or Complex (CNTF + CNTFR{alpha}). Reverse transcription-PCR analysis indicated that C6 cells express CNTF mRNA but not CNTFR{alpha} mRNA. When cells were exposed to the above agents, only Complex caused an up-regulation of connexin43 protein (based on immunocytochemical and immunoblot analysis). Furthermore, Complex increased gap junctional coupling in C6 cells as noted by the passage of the gap junction permeable dye calcein. Finally, it was demonstrated that Complex-treatment reduces the growth rate of C6 cells compared with all of the other agents tested. Taken together, this study has demonstrated that CNTF in combination with its soluble receptor can increase connexin43 expression, increase gap junctional coupling, and reduce the in vitro proliferation of C6 glioma cells.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2002 by the American Association for Cancer Research.