Transcriptional control of the human high mobility group A1 gene: Basal and oncogenic Ras-regulated expression

Isabelle Cleynen, Christel Huysmans, Takehiko Sasazuki, Senji Shirasawa, Wim Van De Ven, Kristel Peeters

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Several studies have already shown that the high mobility group A1 (HMGA1) gene is up-regulated in most common types of cancer and immortalized tissue culture cell lines. HMGA1 expression is also much higher during embryonic development than in adult life. The elevated expression of HMGA1 in cancer thus likely occurs through oncofetal transcriptional mechanisms, which to date have not been well characterized. In the present study, we have cloned and functionally analyzed the TATA-less 5′-flanking regulatory region of human HMGA1. We identified two proximal regulatory regions that are important for basal transcription and in which specificity protein 1 (SP1) and activator protein 1 (AP1) transcription factors seem to be the regulating elements. In addition, we showed that the HMGA1 promoter is strongly inducible by oncogenic Ras, via a distal regulatory region. An AP1 site and three SP1-like sites are responsible for this inducible activity. An even more convincing finding for a role of oncogenic Ras in the regulation of HMGA1 in cancers is the discovery that HMGA1 up-regulation in the HCT116 colon cancer cell line is abolished when the mutated Ras allele is removed front these cells. Our data constitute the first extensive study of the regulation of basal and Ras-induced human HMGA1 gene expression and suggest that the elevated expression of HMGA1 in cancer cells requires, among others, a complex cooperation between SP1 family members and AP1 factors by the activation of Ras GTPase signaling.

Original languageEnglish
Pages (from-to)4620-4629
Number of pages10
JournalCancer Research
Volume67
Issue number10
DOIs
Publication statusPublished - May 15 2007
Externally publishedYes

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Nucleic Acid Regulatory Sequences
Transcription Factor AP-1
Genes
Neoplasms
ras Proteins
Cell Line
Proteins
5' Flanking Region
Colonic Neoplasms
Embryonic Development
Transcription Factors
Up-Regulation
Alleles
Gene Expression

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Cleynen, I., Huysmans, C., Sasazuki, T., Shirasawa, S., Van De Ven, W., & Peeters, K. (2007). Transcriptional control of the human high mobility group A1 gene: Basal and oncogenic Ras-regulated expression. Cancer Research, 67(10), 4620-4629. https://doi.org/10.1158/0008-5472.CAN-06-4325

Transcriptional control of the human high mobility group A1 gene : Basal and oncogenic Ras-regulated expression. / Cleynen, Isabelle; Huysmans, Christel; Sasazuki, Takehiko; Shirasawa, Senji; Van De Ven, Wim; Peeters, Kristel.

In: Cancer Research, Vol. 67, No. 10, 15.05.2007, p. 4620-4629.

Research output: Contribution to journalArticle

Cleynen, I, Huysmans, C, Sasazuki, T, Shirasawa, S, Van De Ven, W & Peeters, K 2007, 'Transcriptional control of the human high mobility group A1 gene: Basal and oncogenic Ras-regulated expression', Cancer Research, vol. 67, no. 10, pp. 4620-4629. https://doi.org/10.1158/0008-5472.CAN-06-4325
Cleynen, Isabelle ; Huysmans, Christel ; Sasazuki, Takehiko ; Shirasawa, Senji ; Van De Ven, Wim ; Peeters, Kristel. / Transcriptional control of the human high mobility group A1 gene : Basal and oncogenic Ras-regulated expression. In: Cancer Research. 2007 ; Vol. 67, No. 10. pp. 4620-4629.
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