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IGF‐II Binding to Insulin Receptor Isoform A Induces a Partially Different Gene Expression Profile from Insulin Binding
Author(s) -
PANDINI GIUSEPPE,
CONTE ENRICO,
MEDICO ENZO,
SCIACCA LAURA,
VIGNERI RICCARDO,
BELFIORE ANTONINO
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1322.053
Subject(s) - insulin , insulin receptor , gene isoform , receptor , gene expression , biology , gene , endocrinology , insulin like growth factor 2 , insulin like growth factor , medicine , microarray analysis techniques , growth factor , insulin resistance , genetics
A bstract : 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.