Mutant p53 accumulates in cycling and proliferating cells in the normal tissues of p53 R172H mutant mice

摘要: // Amanda M. Goh 1,* , Yuezhen Xue Marc Leushacke 2 Ling Li 1 Julin S. Wong Poh Cheang Chiam Siti Aishah Binte Rahmat Michael B. Mann 3,5 Karen Nick Barker Guillermina Lozano 4 Tamara Terzian and David P. Lane p53 Laboratory, A*STAR, Singapore Institute of Medical Biology, 3 Molecular Cell Department Genetics, The University Texas MD Anderson Cancer Center, Houston, TX, USA 5 Research Program, Houston Methodist Institute, * These authors have contributed equally to this work Correspondence to: Lane, email: Keywords : mutant p53, R172H mouse model, small intestine, proliferation, Mdm2 inhibitor, Pathology Received June 25, 2015 Accepted July 05, Published 22, Abstract tumour suppressor is regulated primarily at the protein level. In normal tissues its levels are maintained a very low level by action specific E3 ligases ubiquitin proteosome pathway. contributes transformation, metastasis drug resistance. High can be found in tumours accumulation has previously been reported pathologically cells human skin. We show for first time that similarly elevated detected apparently knock-in model. fact, spontaneously accumulates manner dependent on gene dosage cell type. Mutant wild type which accumulate rapidly after induction ionising radiation or inhibitors, however, clearance much slower than p53. murine intestine limited cycling, crypt base columnar proliferative zone lost as differentiate exit cycle. Loss results even higher expression but still restricted proliferating intestine. Therefore, these mice an experimental system we dissect molecular pathways leading accumulation, important implications cancer prevention therapy.