Insulin-like growth factor-1 inscribes a gene expression profile for angiogenic factors and cancer progression in breast epithelial cells.
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.
Oh
J S
JS
Laboratory of Molecular Carcinogenesis, Hormones and Cancer Group, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, USA.
Kucab
J E
JE
Bushel
P R
PR
Martin
K
K
Bennett
L
L
Collins
J
J
DiAugustine
R P
RP
Barrett
J C
JC
Afshari
C A
CA
Dunn
S E
SE
D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D018450:Disease Progression; D016228:Endothelial Growth Factors / Q000378:metabolism; D004848:Epithelium / Q000473:pathology*; D053222:Fas Ligand Protein; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics*; D008222:Lymphokines / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D017362:Cyclic AMP Response Element-Binding Protein; D016228:Endothelial Growth Factors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008222:Lymphokines; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D007334:Insulin-Like Growth Factor I; D014568:Urokinase-Type Plasminogen Activator