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Double-Stranded Ribonucleic Acid Decreases C6 Rat Glioma Cell Numbers: Effects on Insulin-Like Growth Factor I Gene Expression and Action¹

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

Poly(IC), a synthetic double-stranded RNA copolymer of inosinic and cytidilic acids, decreases the growth of normal and tumorigenic cells. We tested the hypothesis that Poly(IC) decreases C6 glioma cell growth by disrupting an autocrine insulin-like growth factor I (IGF-I) growth loop. Addition of Poly(IC) decreased C6 cell number in confluent and sparse cultures in a dose-dependent manner. Addition of exogenous IGF-I partially compensated for the decrease in cell number caused by Poly(IC) in confluent and subconfluent cultures of C6 cells, suggesting that one mechanism of Poly(IC) action is through down-regulation of IGF-I gene expression and/or action. Treatment of confluent C6 cells with 10 and 200 µg/ml Poly(IC) for 24 h decreased IGF-I messenger RNA (mRNA) levels to 50% and 25% of the control value, respectively. Treatment of C6 cells with 200 µg/ml Poly(IC) for 24 h reduced IGF-I receptor mRNA levels to 50% of the control level. IGF-binding protein-1 (IGFBP-1), -2, and -6 mRNAs were not expressed in the C6 cells used in this study. Treatment of C6 cells with 200 µg/ml Poly(IC) for 24 h reduced IGFBP-4 mRNA and IGFBP-5 mRNA levels to 26% and 29% of the control level, respectively. There was no significant change in IGFBP-3, insulin receptor, or actin mRNA levels with Poly(IC) treatment. Treatment of confluent C6 cells with 200 µg/ml Poly(IC) for 24 h decreased levels of immunoreactive IGF-I in conditioned medium (CM) to 55% of the control value, decreased IGF-I receptor ß-subunit levels to 28% of the control value, and decreased levels of IGFBP-3, IGFBP-4, and IGFBP-5 protein in CM to 45%, 50%, and 30% of the control values, respectively. There was no significant change in actin and tubulin protein levels with Poly(IC) treatment. These results suggest that IGF-I gene expression is down-regulated by Poly(IC) treatment and that IGF-I bioavailability and action in C6 cells are also altered due to decreases in IGF-I receptor and binding protein levels.

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				M. S. Chacko, X. Ma, and M. L. Adamo 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 Endocrinology, June 1, 2002; 143(6): 2144 - 2154. [Abstract] [Full Text] [PDF]

				M. S. Chacko and M. L. Adamo Double-Stranded RNA Decreases IGF-I Gene Expression in a Protein Kinase R-Dependent, but Type I Interferon-Independent, Mechanism in C6 Rat Glioma Cells Endocrinology, February 1, 2002; 143(2): 525 - 534. [Abstract] [Full Text] [PDF]

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