Insulin-like growth factor-1 inscribes a gene expression profile for angiogenic factors and cancer progression in breast epithelial cells.

Abstract:

:Activation of the insulin-like growth factor-1 receptor (IGF-1R) by IGF-1 is associated with the risk and progression of many types of cancer, although despite this it remains unclear how activated IGF-1R 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 P450 1A1, cytochrome P450 1B1, 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.

journal_name

Neoplasia

authors

Oh JS,Kucab JE,Bushel PR,Martin K,Bennett L,Collins J,DiAugustine RP,Barrett JC,Afshari CA,Dunn SE

doi

10.1038/sj.neo.7900229

keywords:

subject

Has Abstract

pub_date

2002-05-01 00:00:00

pages

204-17

issue

3

eissn

1522-8002

issn

1476-5586

journal_volume

4

pub_type

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