癌生物学 （癌基因和 与抑癌基因）.pptx

赵莹珺;提 纲;肿瘤发生机理;;1.癌基因的发现;;Human Bladder Tumor cell line DNA;RESULT: RAS “Activation” is due to a SINGLE point mutation (gly val) at codon 12;2.癌基因定义 Definition;原癌基因特点;;Retroviral promoter/enhancer insertion; Chronic Myelogenous Leukemia (CML)：chromosome 9q34 (c-abl) ? chromosom22q11.2 (bcr)，proto-oncogene c-abl is activated; Gain of multiple copies of defined chromosomal regions (1) Homogeneously staining region (HSR) (2) Double minute chromosomes (DM) ;;;Overview: Classes of oncogenes A. Secreted Growth Factors (e.g. SIS, TGF-α, etc) induce cell growth by mobilisation of energy stores, differentiation and entry into the cell cycle. B. Receptors (cell surface) different cells have different receptors, thereby a signal can produce a response in some cell type but not others Cell surface receptor with protein tyrosine kinase (PTK) activity (erbB, neu/erbB-2, ros, fms) C. Intracellular Transducers act as second messengers which alter transcription, either by allowing new genes to be expressed or by modifying levels of expression of already active genes a- Protein Tyrosine Kinase (src, yes, fps, abl, met ) b- Protein -Serine/Threonine kinases (akt, mos, raf) c- Ras proteins (Ha-ras, Ki-ras, N-ras) d- Adaptors (crk) D. Nuclear Transcription Factors specific binding proteins that recognise short sequence motifs within the promoters and enhancers. These factors then accelerate or retard the rate of initiation of transcripts by RNA polymerase II a- jun, fos b- myc, N-myc, myb, ski, rel;Basic Cellular Signaling Machinery: for example Kinase signaling and Cancer;Growth Factor Receptors;Collection of Receptor protein Tyrosine Kinases (RPTK/RTK);;PTK (Proto-oncogene);;PTK (Proto-oncogene);Src Structure;Basal Activty (discerned from crystal structure);PI-3-kinase;RAS superfamly;RAS signaling ;The World According to RAS;RAS mutation and Cancer;;;;PI3K and MEK pathway in cancer;1. c-myc,