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

Chiara Gorrini, Massimo Squatrito, Chiara Luise, Nelofer Syed, Daniele Perna, Landon Wark, Francesca Martinato, Domenico Sardella, Alessandro Verrecchia, Samantha Bennett, Stefano Confalonieri, Matteo Cesaroni, Francesco Marchesi, Milena Gasco, Eugenio Scanziani, Maria Capra, Sabine Mai, Paolo Nuciforo, Tim Crook, John Lough and Bruno Amati ()
Additional contact information
Chiara Gorrini: European Institute of Oncology (IEO)
Massimo Squatrito: European Institute of Oncology (IEO)
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)

Nature, 2007, vol. 448, issue 7157, 1063-1067

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.

Date: 2007
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DOI: 10.1038/nature06055

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