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Imprinted M6p/Igf2 receptor is mutated in rat liver tumors

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Abstract

We have previously shown that inactivation of mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) is a common early event in both human liver and breast carcinogenesis. The M6p/Igf2r is imprinted in mice while expression is biallelic in most humans. In this investigation the M6p/Igf2r gene is shown to also be imprinted in the liver of Fischer 344, Lewis and Brown Norway rats. In addition, we have identified mutations in the expressed allele of the M6p/Igf2r in 40% of diethylnitrosamine-initiated rat liver tumors. These results provide further evidence that the M6P/IGF2R functions as a liver tumor suppressor gene. They also suggest that mice and rats would be more sensitive than humans to those hepatocarcinogens in which the M6p/Igf2r is mechanistically involved in transformation since one rather than two alleles would need to be inactivated.

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Author notes

  1. JJ Mills & RL Jirtle

    Present address: Department of Pharmacology and Toxicology, Imperial College School of Medicine at St. Mary's, Paddington, W2 1PG, London

Authors and Affiliations

  1. Department of Radiation Oncology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    JJ Mills, JG Falls & RL Jirtle

  2. Department of Safety of Medicines, Zeneca Pharmaceuticals, Alderley Park, Macclesfield, SK10 4TG, Cheshire, UK

    AT De Souza

  3. Molecular Toxicology Group, Glaxo Wellcome Research & Development, Park Road, Ware, SG12 0DP, Herts

    AT De Souza

Authors
  1. JJ Mills
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  2. JG Falls
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  3. AT De Souza
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  4. RL Jirtle
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Mills, J., Falls, J., De Souza, A. et al. Imprinted M6p/Igf2 receptor is mutated in rat liver tumors. Oncogene 16, 2797–2802 (1998). https://doi.org/10.1038/sj.onc.1201801

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  • DOI: https://doi.org/10.1038/sj.onc.1201801

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