Chapter6Neoplasia.ppt

Section 12 Etiology and Oncogenesis of Tumors 1. Molecular Basis of Tumor Nonlethal genetic damage lies at the core of carcinogenesis Four classes of regulatory genes, protooncogene, cancer suppressor gene, regulated apoptosis gene, and DNA repair gene, are the principal targets of genetic damage. Carcinogenesis is a multistep process at both the phenotypic and genetic levels. (1) Oncogenes and cancer ① Protein products of oncogenes a. Growth factors b. Growth factors receptors c. Signal transducing proteins d. Nuclear transcription proteins e. Cyclones and cyclic-dependent kinases ② Activation of oncogenes a. Point mutations b. Chromosome rearrangements Translocations Inversions C. amplification Table Selected oncogenes their mode of activation and associated human tumors 几种常见的癌基因及其激活方式和相关的人类肿瘤 编码的蛋白质 原癌基因 激活机制 相关人类肿瘤 生长因子： PDGF-β链 sis 过度表达 星形细胞瘤、骨肉瘤 FGF HST-1 过度表达 胃癌 INT-2 扩增 　 膀胱癌、乳腺癌、黑色素瘤 TGF-α TGF-α 过度表达 星形细胞瘤、肝细胞癌 HGF HGF 过度表达 甲状腺癌 生长因子受体： EGF受体家族 erb-B1（ECFR） 过度表达 肺鳞癌、神经胶质瘤 erb-B2 扩增 乳腺癌、卵巢癌 CSF-1受体 FMS 点突变 白血病 神经营养因子受体 RET 点突变 多发性内分泌瘤病2A和B， 家族性甲状腺髓样癌 PDGF受体 PDGF-R 过度表达