normal proliferation and tumorigenesis but impaired pancreatic function in mice lacking the cell cycle regulator sei1正常增殖和肿瘤发生但胰腺功能受损的老鼠缺乏细胞周期调节sei1.pdfVIP

Normal Proliferation and Tumorigenesis but Impaired Pancreatic Function in Mice Lacking the Cell Cycle Regulator Sei1 1 1 2,3 4 Pablo J. Fernandez-Marcos , Cristina Pantoja , Agueda Gonzalez-Rodriguez , Nicholas Martin , 5 2,3 4 1 Juana M. Flores , Angela M. Valverde , Eiji Hara , Manuel Serrano * 1Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain, 2 Institute of Biomedicine Alberto Sols (CSIC/UAM), Madrid, Spain, 3 Centro ´ ´ ´ de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), ISCIII, Madrid, Spain, 4 Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo, Japan, 5 Department of Animal Surgery and Medicine, Complutense University of Madrid, Madrid, Spain Abstract Sei1 is a positive regulator of proliferation that promotes the assembly of Cdk4-cyclin D complexes and enhances the transcriptional activity of E2f1. The potential oncogenic role of Sei1 is further suggested by its overexpression in various types of human cancers. To study the role of Sei1, we have generated a mouse line deficient for this gene. Sei1-null fibroblasts did not show abnormalities regarding proliferation or susceptibility to neoplastic transformation, nor did we observe defects on Cdk4 complexes or E2f activity. Sei1-null mice were viable, did not present overt pathologies, had a normal lifespan, and had a normal susceptibility to spontaneous and chemi