The HMGA1 protoncogene frequently deregulated in cancer is a transcriptional target of E2F1

Isabella Massimi, Francesca Guerrieri, Marialaura Petroni, Veronica Veschi, Silvia Truffa, Isabella Screpanti, Luigi Frati, Massimo Levrero, Alberto Gulino, Giuseppe Giannini

Research output: Contribution to journalArticle

Abstract

Reactivation of the HMGA1 protoncogene is very frequent in human cancer, but still very little is known on the molecular mechanisms leading to this event. Prompted by the finding of putative E2F binding sites in the human HMGA1 promoter and by the frequent deregulation of the RB/E2F1 pathway in human carcinogenesis, we investigated whether E2F1 might contribute to the regulation of HMGA1 gene expression. Here we report that E2F1 induces HMGA1 by interacting with a 193bp region of the HMGA1 promoter containing an E2F binding site surrounded by three putative Sp1 binding sites. Both gain and loss of function experiments indicate that Sp1 functionally interacts with E2F1 to promote HMGA1 expression. However, while Sp1 constitutively binds HMGA1 promoter, it is the balance between different E2F family members that tunes the levels of HMGA1 expression between quiescence and proliferation. Finally, we found increased HMGA1 expression in pituitary and thyroid tumors developed in Rb+/- mice, supporting the hypothesis that E2F1 is a novel important regulator of HMGA1 expression and that deregulation of the RB/E2F1 path might significantly contribute to HMGA1 deregulation in cancer.

Original languageEnglish
Pages (from-to)526-534
Number of pages9
JournalMolecular Carcinogenesis
Volume52
Issue number7
DOIs
Publication statusPublished - Jul 2013

Keywords

  • Carcinogenesis
  • HMGA1 promoter
  • Sp1
  • Transcription

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

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  • Cite this

    Massimi, I., Guerrieri, F., Petroni, M., Veschi, V., Truffa, S., Screpanti, I., Frati, L., Levrero, M., Gulino, A., & Giannini, G. (2013). The HMGA1 protoncogene frequently deregulated in cancer is a transcriptional target of E2F1. Molecular Carcinogenesis, 52(7), 526-534. https://doi.org/10.1002/mc.21887