335. Global Transcriptional Profiles of Murine C2C12 Myoblasts Treated with IGF-1

These studies were intended to characterize the mechanisms of action of insulin-like growth factor (IGF-1) in myoblasts. Toward that end, we exposed cultures of murine C2C12 myoblasts to IGF-1 and examined the global gene expression profiles of the cells using a high-density oligonucleotide array platform (Affymetrix, mouse 430A) containing about 22,600 probe sets. We identified approximately 94, 180 and 221 genes that were up-regulated at least two fold relative to control cells (zero time point) at 1, 2 and 4 hours respectively. In addition, we identified approximately 48, 111 and 107 genes that were down-regulated more than two fold at the same times following IGF-1 treatment. Of special interest is the fact that the up-regulated genes include several genes that belong to the cholesterol biosynthetic pathway, such as hydroxysteroid (17 beta) dehydrogenase 7, lanosterol synthase, CYP 51, isopentenyl-diphosphate delta isomerase, 3-hydroxy-3-methylglutaryl- Coenzyme A synthase 1, phosphomevalonate kinase and farnesyl diphosphate farnesyl transferase 1, all of which are induced by 3-5 fold, suggesting the involvement of a common trans-acting factor(s). Two candidates for such a common trans-acting factor(s) are suggested by the slight but reproducible (ca. 1.5 fold) degree of over-expression following IGF-1 treatment of Sterol Regulatory Element Binding Protein (SREBP2) and SREBP Cleavage Associated Protein (SCAP) mRNAs. Even a slight change in the expression of these trans-acting factors themselves might elicit a more marked change in the expression of their target genes. We are further characterizing the effect IGF-1 on the steroid and other selected pathways in C2C12 cells.