Tumor pathogenesis 陈玮副教授 Email:chenwei566@zju.edu.cn 个人主页http:/mypage.zju.edu.cn/5668888
1 Tumor pathogenesis 陈玮 副教授 Email：chenwei566@zju.edu.cn 个人主页： http://mypage.zju.edu.cn/566 8888
Tumor pathogenesis ◆ Oncogenes Tumor suppressor genes Invasion and metastasis
Tumor pathogenesis ◆ Oncogenes ◆ Tumor suppressor genes ◆ Invasion and Metastasis
Introduction a Carcinogensis is multistep process involving the multiple genetic changes including the activation of cooperating oncogenes and the inactivation of tumor suppressors in somatic cells Initiation Promotion Conversion Progression Defects in Terminal Differentiation Defects in Growth Control Resistance to Cytotoxicity Defects in Programmed Cell Death D =)A oNvRUs NORMAL CELL NITIATED ENEOPLASTIC CLINICAL CANCER CELL LESION CANCER METASTASIS Activation of Proto-Oncogenes e Inactivation of Tumor Suppressor Genes Inactivation of Antimetastasis Genes Cancer Susceptibility Genes
3 Introduction Carcinogensis is multistep process involving the multiple genetic changes including the activation of cooperating oncogenes and the inactivation of tumor suppressors in somatic cells
Molecular alterations during human colon tumor progression DNA(~40-50%) hypomethylation (~60%) (~90%) activation loss of loss of Apc of K-ras 18q TSG loss of p53w50-70 % normal _hyperplastic early+intermediate +late i carcinoma invasion epithelium epithelium adenomas metastasis The precise contribution of hypomethylation to tumor progression remains unclear some evidence suggests that it creates chromosomal instability
Molecular alterations during human colon tumor progression The precise contribution of hypomethylation to tumor progression remains unclear; some evidence suggests that it creates chromosomal instability. (~ 90 %) (~ 40-50 %) (~ 50-70 %) (~ 60 %) * *
Molecular Basis of Multistep Carcinogenesis NORMAL COLONIC EPITHELIUM Homozygous loss of APC locus on 5q Mutation of ras on 12p Cells proliferate and form an adenoma Homozygous loss of DCC on 18q More proliferation, larger adenoma cells look abnormal Homozygous loss of p53 on 17p INVASIVE CARCINOMA
Molecular Basis of Multistep Carcinogenesis