IGF-II binding to insulin receptor isoform A induces a partially different gene expression profile from insulin binding

Giuseppe Pandini, Enrico Conte, Enzo Medico, Laura Sciacca, Riccardo Vigneri, Antonino Belfiore

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)450-456
Number of pages7
JournalAnnals of the New York Academy of Sciences
Volume1028
DOIs
Publication statusPublished - 2004

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Keywords

  • Gene expression
  • Insulin
  • Insulin receptor
  • Insulin receptor isoform A
  • Insulin-like growth factor-II
  • Microarray
  • Real-time PCR

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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