Loss of Imprinting of <i>Igf2</i> Alters Intestinal Maturation and Tumorigenesis in Mice

• Takashi Sakatani

  Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

• Atsushi Kaneda

  Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

• Christine A. Iacobuzio-Donahue

  Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

• Mark G. Carter

  Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

• Sten de Boom Witzel

  Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

• Hideyuki Okano

  Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

• Minoru S. H. Ko

  Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

• Rolf Ohlsson

  Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

• Dan L. Longo

  Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

• Andrew P. Feinberg

  Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

Loss of imprinting (LOI) of the insulin-like growth factor II gene ( IGF2 ) is an epigenetic alteration that results in a modest increase in IGF2 expression, and it is present in the normal colonic mucosa of about 30% of patients with colorectal cancer. To investigate its role in intestinal tumorigenesis, we created a mouse model of Igf2 LOI by crossing female H19 +/– mice with male Apc +/Min mice. Mice with LOI developed twice as many intestinal tumors as did control littermates. Notably, these mice also showed a shift toward a less differentiated normal intestinal epithelium, reflected by an increase in crypt length and increased staining with progenitor cell markers. A similar shift in differentiation was seen in the normal colonic mucosa of humans with LOI. Thus, altered maturation of nonneoplastic tissue may be one mechanism by which epigenetic changes affect cancer risk.

Journal

• Science

  Science 307 (5717), 1976-1978, 2005-03-25

  American Association for the Advancement of Science (AAAS)

Keywords

• Multidisciplinary

Details

• CRID: 1363951795944594816
• NII Article ID: 80017367156
• DOI: 10.1126/science.1108080
• ISSN: 10959203
• ISSN: 00368075
• ISSN: http://id.crossref.org/issn/00368075
• Web Site: https://www.science.org/doi/pdf/10.1126/science.1108080
• Data Source:
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  • CiNii Articles
  • KAKEN