Insulin-Like Growth Factor-1 Inscribes a Gene Expression Profile for Angiogenic Factors and Cancer Progression in Breast Epithelial Cells

• Main Authors: J.S. Oh, J.E. Kucab, P.R. Bushel, K. Martin, L. Bennett, J. Collins, R.P. DiAugustine, J.C. Barrett, C.A. Afshari, S.E. Dunn
• Format: Article
• Language: English
• Published: Elsevier 2002-01-01
• Series: Neoplasia: An International Journal for Oncology Research
• Subjects: microarray; insulin-like growth factor-1 receptor; AKT; transcription factors; breast cancer
• Online Access: http://www.sciencedirect.com/science/article/pii/S1476558602800148
• ISSN: 1476-5586; 1522-8002

Activation of the insulin-like growth factor-1 receptor (IGF-11R) by IGF-1 is associated with the risk and progression of many types of cancer, although despite this it remains unclear how activated IGF-1 R contributes to cancer progression. In this study, gene expression changes elicited by IGF-1 were profiled in breast epithelial cells. We noted that many genes are functionally linked to cancer progression and angiogenesis. To validate some of the changes observed, the RNA and/or protein was confirmed for c-fos, cytochrome P4501Al, cytochrome P450 1131, interleukin-1 beta, fas ligand, vascular endothelial growth factor, and urokinase plasminogen activator. Nuclear proteins were also temporally monitored to address how gene expression changes were regulated. We found that IGF-1 stimulated the nuclear translocation of phosphorylated AKT, hypoxic-inducible factor-1 alpha, and phosphorylated cAMP-responsive element-binding protein, which correlated with temporal changes in gene expression. Next, the promoter regions of IGF-1-regulated genes were searched in silico. The promoters of genes that clustered together had similar regulatory regions. In summary, IGF-1 inscribes a gene expression profile relevant to cancer progression, and this study provides insight into the mechanism(s) whereby some of these changes occur.