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). 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.
Pandini
Giuseppe
G
Dipartimento di Medicina Interna e di Medicine Specialistiche, Università di Cantania, Italy.
Conte
Enrico
E
Medico
Enzo
E
Sciacca
Laura
L
Vigneri
Riccardo
R
Belfiore
Antonino
A
D000818:Animals; D005347:Fibroblasts / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D011972:Receptor, Insulin / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D007328:Insulin; D008024:Ligands; D020033:Protein Isoforms; D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II; D011972:Receptor, Insulin