病理学英文课件：Neoplasia.ppt

MICROBIAL CARCINOGENESIS Oncogenic DNA Viruses Human papilloma virus (HPV) Epstein-Barr virus (EBV) Hepatitis B virus (HBV) Kaposi sarcoma herpesvirus (human herpesvirus 8) Oncogenic RNA Viruses Human T-Cell Leukemia Virus Type 1 Examples of Tumor Viruses Viruses Tumors Genome (kb) Distribution DNA virus HBV HCC 3 southeast Asia HPV warts, ca 5 global EBV NPC 100-200 southern China Burkitt’s west Africa lymphoma RNA virus HTLV-1 HTL 9 Japan ESSENTIAL ALTERATIONS FOR MALIGNANT TRANSFORMATION Self-sufficiency in growth signals usually as a consequence of oncogene activation Insensitivity to growth-inhibitory signals Evasion of apoptosis as a consequence of inactivation of p53 Limitless replicative potential Telomerase activation ESSENTIAL ALTERATIONS FOR MALIGNANT TRANSFORMATION Sustained angiogenesis Ability to invade and metastasize Defects in DNA repair Immune surveillance and escape SELF-SUFFICIENCY IN GROWTH SIGNALS: ONCOGENES Genes that promote autonomous cell growth in cancer cells are called oncogenes Their unmutated cellular counterparts are called proto-oncogenes Oncogenes are created by mutations in proto-oncogenes and are characterized by the ability to promote cell growth in the absence of normal growth-promoting signals Their products are called oncoproteins DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature 260: 176-173 (1976) v-src oncogene derives from c-src proto-oncogene and contains mutation(s) that renders it hyperactive and unregulated Oncogenes Mutations convert proto-oncogenes into constitutively active cellular oncogenes that are involved in tumor development because the oncoproteins they encode endow the cell with self-sufficien