This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chacko, M. S. Articles by Adamo, M. L. Search for Related Content PubMed PubMed Citation Articles by Chacko, M. S. Articles by Adamo, M. L.

Double-Stranded Ribonucleic Acid Decreases C6 Rat Glioma Cell Proliferation in Part by Activating Protein Kinase R and Decreasing Insulin-Like Growth Factor I Levels

Department of Biochemistry, University of Texas Health Science Center, San Antonio, Texas 78229-3900

Address all correspondence and requests for reprints to: Martin L. Adamo, Ph.D., Department of Biochemistry, Mail Code 7760, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900. E-mail: . adamo{at}biochem.uthscsa.edu

We previously reported that reduction of autocrine IGF-I by polyinosinic-polycytidylic acid [poly(IC)] was permissive for the poly(IC)-mediated decrease in C6 rat glioma cell number. We now report that poly(IC) caused a block in G₁ to S transition in confluent C6 cultures, whereas in subconfluent cultures, poly(IC) decreased the percentage of cells in the G₂/M phase. Addition of IGF-I to poly(IC)-treated cells decreased the percentage of cells in G₀/G₁ phase and increased the percentage of cells in G₂/M phase in confluent and subconfluent C6 cultures, indicating the reversal of cell cycle blocks. Inhibition of protein kinase R (PKR) activation partially prevented the poly(IC)-mediated cytostasis of C6 cells. Poly(IC) induced interferon- in C6 cells. Both IGF-I and a blocking antibody against type I interferon (IFN) prevented the increase in PKR levels and the decrease in cell proliferation caused by poly(IC). We conclude that poly(IC) induces IFN, which mediates the cytostatic effect of poly(IC) on C6 cells at least in part through PKR. IGF-I prevents IFN from inducing PKR, thus explaining the ability of IGF-I to reverse the cell cycle blocks and the decreased C6 proliferation caused by poly(IC).

This article has been cited by other articles:

				F. Lefranc, J. Brotchi, and R. Kiss Possible Future Issues in the Treatment of Glioblastomas: Special Emphasis on Cell Migration and the Resistance of Migrating Glioblastoma Cells to Apoptosis J. Clin. Oncol., April 1, 2005; 23(10): 2411 - 2422. [Abstract] [Full Text] [PDF]

				G. Cangemi, B. Morandi, A. D'Agostino, C. Peri, R. Conte, G. Damonte, G. Ferlazzo, R. Biassoni, and G. Melioli IFN-{alpha} mediates the up-regulation of HLA class I on melanoma cells without switching proteasome to immunoproteasome Int. Immunol., December 1, 2003; 15(12): 1415 - 1421. [Abstract] [Full Text] [PDF]