IGF-II Binding to Insulin Receptor Isoform A Induces a Partially Different Gene Expression Profile from Insulin Binding

: Insulin receptor isoform A (IR‐A) is a fetal insulin receptor isoform that is overexpressed in cancer. We investigated whether insulin‐like growth factor (IGF)‐II may elicit a different gene expression response from insulin in cells expressing only IR‐A and lacking IGF‐I receptor (R−/IR‐A cells)....

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Bibliographic Details
Published in:Annals of the New York Academy of Sciences 2004-12, Vol.1028 (1), p.450-456
Main Authors: PANDINI, GIUSEPPE, CONTE, ENRICO, MEDICO, ENZO, SCIACCA, LAURA, VIGNERI, RICCARDO, BELFIORE, ANTONINO
Format: Article
Language:English
Subjects:
Animals
Fibroblasts - metabolism
gene expression
Gene Expression Regulation, Neoplastic
Humans
insulin
Insulin - metabolism
insulin receptor
insulin receptor isoform A
Insulin-Like Growth Factor II - metabolism
insulin-like growth factor-II
Ligands
Mice
microarray
Oligonucleotide Array Sequence Analysis
Protein Binding
Protein Isoforms
real-time PCR
Receptor, Insulin - chemistry
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
Time Factors
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Summary:: Insulin receptor isoform A (IR‐A) is a fetal insulin receptor isoform that is overexpressed in cancer. We investigated whether insulin‐like growth factor (IGF)‐II may elicit a different gene expression response from insulin in cells expressing only IR‐A and lacking IGF‐I receptor (R−/IR‐A cells). Cells were stimulated with either insulin or IGF‐II (at 0.5, 3, and 8 h), and global gene expression was studied by microarray technology. Results were validated by quantitative real‐time PCR. We found that 214 transcripts were similarly regulated by insulin and IGF‐II, whereas 45 transcripts were differentially regulated. of these 45 genes, 18 were responsive to only one of the two ligands (12 to insulin and 6 to IGF‐II). Twenty‐seven transcripts were regulated by both ligands but with a significant difference at at least one time point. IGF‐II was a more potent regulator than insulin for these genes. In conclusion, insulin and IGF‐II, acting via the same receptor (IR‐A), may differentially affect gene expression in cells. These findings provide a molecular basis in clarifying the biological role of IR‐A in embryonic/fetal life and in cancer.
ISSN:0077-8923
1749-6632
DOI:10.1196/annals.1322.053