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Tip60 is a haplo-insufficient tumour suppressor required for an oncogene-induced DNA damage response

Author

Listed:
  • Chiara Gorrini

    (European Institute of Oncology (IEO))

  • Massimo Squatrito

    (European Institute of Oncology (IEO)
    Present address: Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.)

  • Chiara Luise

    (FIRC Institute of Molecular Oncology (IFOM), IFOM-IEO Campus, Milan 20139, Italy)

  • Nelofer Syed

    (Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories, London, SW3 6JB, UK)

  • Daniele Perna

    (European Institute of Oncology (IEO))

  • Landon Wark

    (Manitoba Institute of Cell Biology and The Genomic Center for Cancer, Research and Diagnosis, CancerCare Manitoba, University of Manitoba, Winnipeg, Manitoba R3E 0V9, Canada)

  • Francesca Martinato

    (European Institute of Oncology (IEO))

  • Domenico Sardella

    (European Institute of Oncology (IEO))

  • Alessandro Verrecchia

    (European Institute of Oncology (IEO))

  • Samantha Bennett

    (European Institute of Oncology (IEO))

  • Stefano Confalonieri

    (FIRC Institute of Molecular Oncology (IFOM), IFOM-IEO Campus, Milan 20139, Italy)

  • Matteo Cesaroni

    (European Institute of Oncology (IEO))

  • Francesco Marchesi

    (Hygiene and Public Health, Section of Veterinary and Avian Pathology, University of Milan)

  • Milena Gasco

    (San Croce e Carle Hospital)

  • Eugenio Scanziani

    (Hygiene and Public Health, Section of Veterinary and Avian Pathology, University of Milan)

  • Maria Capra

    (FIRC Institute of Molecular Oncology (IFOM), IFOM-IEO Campus, Milan 20139, Italy)

  • Sabine Mai

    (Manitoba Institute of Cell Biology and The Genomic Center for Cancer, Research and Diagnosis, CancerCare Manitoba, University of Manitoba, Winnipeg, Manitoba R3E 0V9, Canada)

  • Paolo Nuciforo

    (FIRC Institute of Molecular Oncology (IFOM), IFOM-IEO Campus, Milan 20139, Italy)

  • Tim Crook

    (Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Chester Beatty Laboratories, London, SW3 6JB, UK)

  • John Lough

    (Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA)

  • Bruno Amati

    (European Institute of Oncology (IEO))

Abstract

Tip60 as an oncogene The acetyl-transferase Tip60 regulates transcription and is involved in the DNA damage response. Now it has been found to have tumour suppressor activity in vivo both in a mouse model and in human tumours. The human Tip60 locus (HTATIP) is frequently mutated in head and neck squamous cell carcinoma, breast carcinoma and lymphomas. Nuclear Tip60 staining on tissue microarrays is lost in a variety of tumours, and most significantly in breast carcinomas. This work suggests that critical levels of Tip60 are required for mounting an oncogene-induced DNA damage response in incipient tumour cells: the failure of this defence mechanism may synergize with p53 mutation towards tumour progression.

Suggested Citation

  • Chiara Gorrini & Massimo Squatrito & Chiara Luise & Nelofer Syed & Daniele Perna & Landon Wark & Francesca Martinato & Domenico Sardella & Alessandro Verrecchia & Samantha Bennett & Stefano Confalonie, 2007. "Tip60 is a haplo-insufficient tumour suppressor required for an oncogene-induced DNA damage response," Nature, Nature, vol. 448(7157), pages 1063-1067, August.
    • Handle: RePEc:nat:nature:v:448:y:2007:i:7157:d:10.1038_nature06055
    DOI: 10.1038/nature06055
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