cystatin c deficiency promotes epidermal dysplasia in k14-hpv16 transgenic mice半胱氨酸蛋白酶抑制物c缺乏促进k14-hpv16转基因小鼠表皮发育不良.pdf

Cystatin C Deficiency Promotes Epidermal Dysplasia in K14-HPV16 Transgenic Mice 1,2 1,3 1 2 2 1 1 Weifang Yu , Jian Liu , Michael A. Shi , Jianan Wang , Meixiang Xiang , Shiro Kitamoto , Bing Wang , 1 4 1 5 1 Galina K. Sukhova , George F. Murphy , Gabriela Orasanu , Anders Grubb , Guo-Ping Shi * 1 Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America, 2 Department of Cardiology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China, 3 Department of Life Sciences, School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, China, 4 Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America, 5 Department of Clinical Chemistry, University Hospital, Lund, Sweden Abstract Background: Cysteine protease cathepsins are important in extracellular matrix protein degradation, cell apoptosis, and angiogenesis. Mice lacking cathepsins are protected from tumor progression in several animal models, suggesting that the regulation of cathepsin activities controls the growth of various malignant tumors. Methods and Results: We tested the role of cathepsins using a mouse model of multistage epithelial carcinogenesis, in which the human keratin-14 promoter/enhancer drove the expression of human papillomavirus type 16 (HPV16) early region E6/E7 transgenes. During the progression of premalignant dysplasia, we observed increased expression of cysteine protease cathepsin S, but concomitantly reduc