genetic ablation of bcl-x attenuates invasiveness without affecting apoptosis or tumor growth in a mouse model of pancreatic neuroendocrine cancer的基因消融bcl-x变弱侵袭性没有影响细胞凋亡和肿瘤生长在胰腺神经内分泌肿瘤的小鼠模型.pdfVIP

Genetic Ablation of Bcl-x Attenuates Invasiveness without Affecting Apoptosis or Tumor Growth in a Mouse Model of Pancreatic Neuroendocrine Cancer 1.¤ 1. 2 1 Jeffrey H. Hager , Danielle B. Ulanet , Lothar Hennighausen , Douglas Hanahan * 1 Diabetes and Hellen Diller Family Comprehensive Cancer Centers, Department of Biochemistry Biophysics, University of California San Francisco, San Francisco, California, United States of America, 2 Laboratory of Genetics and Physiology, The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, Maryland, United States of America Abstract Tumor cell death is modulated by an intrinsic cell death pathway controlled by the pro- and anti-apoptotic members of the Bcl-2 family. Up-regulation of anti-apoptotic Bcl-2 family members has been shown to suppress cell death in pre-clinical models of human cancer and is implicated in human tumor progression. Previous gain-of-function studies in the RIP1-Tag2 model of pancreatic islet carcinogenesis, involving uniform or focal/temporal over-expression of Bcl-xL, demonstrated accelerated tumor formation and growth. To specifically assess the role of endogenous Bcl-x in regulating apoptosis and tumor progression in this model, we engineered a pancreatic b-cell-specific knockout of both alleles of Bcl-x using the Cre- LoxP system of homologous recombination. Surprisingly, there was no appreciable effect on tumor cell apoptosis rates or on tumor growth in the Bcl-x knockout mice. Other anti-apoptotic Bcl-2 family members were expressed but not substantively altered at the mRNA level in the Bcl-x-null tumors, sugge