cutaneous squamous cell carcinoma (scc) and the dna damage response patm expression patterns in pre-malignant and malignant keratinocyte skin lesions皮肤鳞状细胞癌(scc)和dna损伤反应patm表达模式3和恶性皮肤角化细胞病变.pdfVIP

Cutaneous Squamous Cell Carcinoma (SCC) and the DNA Damage Response: pATM Expression Patterns in Pre- Malignant and Malignant Keratinocyte Skin Lesions 1 2 1 1 3 4 Ferina Ismail *, Mohamed Ikram , Karin Purdie , Catherine Harwood , Irene Leigh , Alan Storey 1 Centre for Cutaneous Research, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom, 2 Molecular Oncology and Imaging, Institute of Cancer, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom, 3 College of Medicine Dentistry and Nursing, University of Dundee, Dundee, United Kingdom, 4 Department of Molecular Oncology, Wetherall Insitute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom Abstract Recent evidence suggests that an initial barrier to the emergence of tumours is a DNA damage response that evokes a counter-response which arrests the growth of, or eliminates, damaged cells. Early precursor lesions express markers of an activated DNA damage response in several types of tumour, with a diminishing response in more advanced cancers. An important marker of DNA damage is ATM which becomes phosphorylated (pATM) upon activation. We have investigated pATM expression patterns in cultured keratinocytes, skin explants and a spectrum of pre-malignant to malignant keratinocyte skin lesions by immunohistochemistry. We found that pATM was mainly localised to the Golgi apparatus, which contrasts with its nuclear localisation in other tissues. Upon UV irradiation there is transient formation of pATM in nuclear foci, c