wnt signalling pathway parameters for mammalian cellswnt信号通路对哺乳动物细胞参数.pdfVIP

Wnt Signalling Pathway Parameters for Mammalian Cells 1,3* 2 1 1 2 Chin Wee Tan , Bruce S. Gardiner , Yumiko Hirokawa , Meredith J. Layton , David W. Smith , Antony W. Burgess1 1 Ludwig Institute for Cancer Research, Melbourne-Parkville Branch, Parkville, Victoria, Australia, 2 Faculty of Engineering, Computing and Mathematics, The University of Western Australia, Perth, Western Australia, Australia, 3 Melbourne School of Engineering, University of Melbourne, Parkville, Victoria, Australia Abstract Wnt/b-catenin signalling regulates cell fate, survival, proliferation and differentiation at many stages of mammalian development and pathology. Mutations of two key proteins in the pathway, APC and b-catenin, have been implicated in a range of cancers, including colorectal cancer. Activation of Wnt signalling has been associated with the stabilization and nuclear accumulation of b-catenin and consequential up-regulation of b-catenin/TCF gene transcription. In 2003, Lee et al. constructed a computational model of Wnt signalling supported by experimental data from analysis of time-dependent concentration of Wnt signalling proteins in Xenopus egg extracts. Subsequent studies have used the Xenopus quantitative data to infer Wnt pathway dynamics in other systems. As a basis for understanding Wnt signalling in mammalian cells, a confocal live cell imaging measurement technique is developed to measure the cell and nuclear volumes of MDCK, HEK293T cells and 3 human colorectal cancer cell lines and the concentrations of Wnt signalling proteins b-catenin, Axin, APC, GSK3b and E-cadherin. These parameters provide the basis for formulating Wnt signalling models for kidney/intestinal epithelial mammalian