p 63 and epithelial homeostasis Studies of p 63 under normal , hyper - proliferative and malignant conditions

..................................................................................................................... 1 Original Articles.......................................................................................................... 2 Abbreviations .............................................................................................................. 3 Introduction ................................................................................................................ 5 p63 belongs to the p53 family .................................................................................. 5 An older member of the p53 family ....................................................................... 5 Transcriptional regulation similar to p53 ............................................................. 6 Overlapping and distinct functions to p53 ............................................................ 7 p63 is a critical regulator during epithelial morphogenesis ........................................ 8 p63 is essential for maintenance of epithelial homeostasis ...................................... 10 Location in stratified squamous epithelium ........................................................ 10 Maintains basal cell proliferation and prevents premature differentiation ........... 11 Induces terminal differentiation ......................................................................... 13 Regulates adhesion and maintains integrity of basal membrane .......................... 13 Responds to DNA damage .................................................................................. 14 Contributes to cellular senescence and aging ..................................................... 15 Contributes to carcinogenesis ............................................................................ 16 Psoriasis ................................................................................................................ 17 Epidemiology, symptoms and histological features ............................................. 17 Genetic and environmental triggers ................................................................... 19 Pathogenesis and treatment ............................................................................... 19 Phototherapy ..................................................................................................... 21 Squamous cell carcinoma of the head and neck ...................................................... 21 Epidemiology and risk factors ............................................................................ 21 Diagnosis and treatment .................................................................................... 22 Molecular mechanisms for carcinogenesis ......................................................... 23 Aims ......................................................................................................................... 24 Materials and Methods .............................................................................................. 25 Paper I and Paper II ............................................................................................... 25 Paper III and Paper IV ........................................................................................... 29 Results and Discussion .............................................................................................. 31 Paper I .................................................................................................................. 31 Paper II ................................................................................................................. 32 Paper III ................................................................................................................ 33 Paper IV ................................................................................................................ 34 General discussion .................................................................................................... 35 Conclusions .............................................................................................................. 38 Acknowledgements ................................................................................................... 39 References ................................................................................................................ 41