肿瘤的分子生物学特征-2008.ppt

肿瘤的分子生物学特征;Molecular Cell Biology of Tumor;A survey course of cancer biology including tumor pathology, initiation, progression and metastasis, genetic instability, DNA damage and repair, cell cycle control, oncogenes and tumor suppressor genes and the immune response. ;Cancer Incidence and Death Rate;Early detection is the key!;;Initiation, Promotion, and Progression;Events in metastasis. ;MOLECULAR CARCINOGENESIS;The Hallmarks of Cancer;General Information;General Information(2);General Information(3);General Information;What causes Cancer? Genetic mutations;;The Oncogene;Mechanisms of Proto-oncogene activation 1. Mutations: * Point mutations/deletions/insertions - most characterized in human trs, frequent in Ras * Causes constitutive activation of the signal  transducing function of Ras protein 2. Gene amplification Results from several rounds of unscheduled DNA synthesis occurring during a single cell cycle - HSR, DM Her2 Breast cacinoma, n-myc neuroblastoma;3. Chromosomal re-arrangement * chromosomal translocations; inversions * Gene activation -transcriptional activation of Proto-oncogenes eg. follicular lymphoma t (14:18) Bcl2 Burkitts lymphoma t (8:14) c-myc * Gene fusion: codes for chimeric protein eg. CML t (9:22) BCR/Abl. APML t(15:17) PML/Rar;Tumorgenesis - ?;Definition for:Oncogene ;Initiation Promotion ;Oncogenes Gene encoding proteins that is essential for the initiation, promotion and progression of the malignant state 100 different oncogenes discovered as the transforming genes of RNA tumour viruses Proto-oncogene counterpart of viral-oncogene - normal cellular genes which encodes proteins to regulate cellular response to external stimuli that controls cellular proliferation and differentiation. - activated by mutation - nomenclature ;Classification of oncogenes 1. Growth factors - sis, ist 2. Growth factor receptors (RTK) - erb B2, f