HMGA1 protein is a positive regulator of the insulin-like growth factor-I receptor gene

Aurora Aiello, Giuseppe Pandini, Rive Sarfstein, Haim Werner, Guidalberto Manfioletti, Riccardo Vigneri, Antonino Belfiore*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The IGF-I receptor (IGF-IR) is often overexpressed in cancer and is believed to play a crucial role in cancer progression. High Mobility Group A1 (HMGA1) is a non-histone chromatin protein that has the ability to regulate gene expression through DNA binding and involvement in enhanceosome complexes. HMGA1 is expressed at low level in adult differentiated cells, whereas it is expressed at high level in embryonic and malignant cells. We evaluated whether the HMGA1 aberrant expression has a role in IGF-IR overexpression in cancer. We found that HMGA1 silencing induces a marked decrease in IGF-IR expression in various human cancer cell lines. Conversely, forced HMGA1 overexpression in cells with low endogenous HMGA1 levels was associated with IGF-IR upregulation. HMGA1 silencing reduced igf-ir promoter activity whereas forced HMGA1 expression increased it. Using the chromatin immunoprecipitation assay, HMGA1 protein was found to bind to the igf-ir promoter. Moreover, HMGA1 was found to associate with both p53 and Sp1, two major regulators of igf-ir gene transcription and to antagonise the p53 inhibitory activity while enhancing the Sp1 stimulatory activity. Our data indicate, therefore, that HMGA1 protein is a positive regulator of IGF-IR expression and that HMGA1 overexpression may contribute to IGF-IR dysregulation in cancer cells.

Original languageEnglish
Pages (from-to)1919-1926
Number of pages8
JournalEuropean Journal of Cancer
Issue number10
StatePublished - Jul 2010


  • HMGA1 protein
  • IGF-IR
  • IGF-IR regulation
  • Insulin receptor


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