Insulin and IGF-1 Induce Different Patterns of Gene Expression in Mouse Fibroblast NIH-3T3 Cells: Identification by cDNA Microarray Analysis

Abstract

The IGF-1 receptor and the related insulin receptor are similar in structure and activate many of the same postreceptor signaling pathways, yet they mediate distinct biological functions. It is still not understood how the specificity of insulin vs. IGF-1 signaling is controlled. In this study, we have used cDNA microarrays to monitor the gene expression patterns that are regulated by insulin and IGF-1. Mouse fibroblast NIH-3T3 cells expressing either the wild-type human IGF receptor or the insulin receptor were stimulated with either IGF-1 or insulin, respectively. Thirty genes, 27 of which were not previously known to be IGF-1 responsive, were up-regulated by IGF-1 but not by insulin. Nine genes, none of which was previously known to be insulin responsive, were up-regulated by insulin but not by IGF-1. The IGF- and insulin-induced regulation of 10 of these genes was confirmed by Northern blot analysis. Interestingly, more than half of the genes up-regulated by IGF-1 are associated with mitogenesis and differentiation, whereas none of the genes specifically up-regulated by insulin are associated with these processes. Our results indicate that under the conditions used in this study, IGF-1 is a more potent activator of the mitogenic pathway than insulin in mouse fibroblast NIH-3T3 cells.

Gene expression profiling of ErbB receptor and ligand-dependent transcription

“…ErbB2Ab treatment favored decreases in transcript levels for genes including phosphatidic acid phosphatase 2A (PPAP2A) and laminin b1, whereas ErbB4Ab had greater effects on genes including AMP-activated protein kinase and H-cadherin. ErbB-induced gene regulation resulted in fewer decreases than increases in transcript levels, consistent with the expression profile analyses of other RTKs (Dupont et al, 2001;Sweeney et al, 2001;Mulligan et al, 2002).…”

“…Table 1 in bold) and PPAP2A, which were preferentially up-and downregulated by ErbB2Ab, respectively, were also confirmed by QRT-PCR as being specific to ErbB2 activation ( Figure 3 Fambrough et al (1999) indicated that activation of platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor, or EGFR resulted in nearly identical patterns of gene regulation. More recently, it has been shown that insulin receptor and insulin-like growth factor receptor-1 regulate an overlapping but distinct group of genes (Dupont et al, 2001(Dupont et al, , 2003Mulligan et al, 2002). Similar results have now been observed between TGFb receptors, ALK1 and ALK5, and two isoforms of the progesterone receptor (Ota et al, 2002;Richer et al, 2002).…”

Differential Morphology and Homogeneity of Tissue-Engineered Cartilage in Hydrodynamic Cultivation with Transient Exposure to Insulin-Like Growth Factor-1 and Transforming Growth Factor-β1

“…Rationally, insulin and IGF-1 are highly similar in the molecular structure, both of which are capable of crossreacting with the insulin receptor and IGF-1R. 38,39 Although each receptor attracts its own ligand with a 100-to-1000-fold higher affinity than that to the other heterologous molecules, 39 it is possible that insulin present in BMinterfered with the binding between IGF-1 and IGF-1R such that the disturbed expression of both molecules was observed. The dose of ITS (1%) employed here has previously been shown by our group to be essential to support the WWB cultivation of neocartilage in the presence of a minimal content of serum.…”

PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells

“…The loss of PTEN is thought to play an important role in tumor cell proliferation and metastasis, due to a lack of control of the signaling pathways that mediate cellular processes such as apoptosis and migration (Huang and Kontos, 2002;Kandel et al, 2002;Pene et al, 2002). We stably PTEN is a dual-specificity phosphatase that can dephosphorylate lipid signaling molecules and proteins involved in tyrosine kinase receptor signaling cascades (Dupont et al, 2001;Yamada and Araki, 2001;Fernandez and Eng, 2002). In a previous study, it was shown that PTEN downregulated cyclin D1 expression through its protein-phosphatase activity and upregulated p27 via its lipid-phosphatase activity in breast cancer cells (Weng et al, 2001a, b).…”