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GKA deel 1 college 7

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  • 1.  
  • 2. Overzicht deel tumoren
    • Hoe ontstaat kanker?
      • Proto-oncogenen
    • Tumor-suppressors
      • Plus DNA repair
      • p53
    • Immunotherapie
    • Apoptose
    • Metastasering
      • Uitzaaiing
    • Angiogenese
      • Nieuwe bloedvaten
    • De zeven processen
      • Overzicht en afsluiting
    Nature 442, 2006, 140
  • 3. How cancer arises Weinberg, Sci Am 275-3, 1996, 32-40
    • Proto-oncogenes
    • Tumor suppressors
    • DNA repair
    • Apoptosis
    • Telomeres
    • Angiogenese
    • Metastasis
  • 4. Progression to invasive tumor Weinberg, Sci Am 275-3, 1996, 32-40
    • Sarcoma: tumour of connective tissue
    • Glioma: tumour of non-neuronal brain cells
    • Carcinoma: tumor of epithelial cells
  • 5. Signal transduction: on and off Weinberg, Sci Am 275-3, 1996, 32-40 Avoid words such as ‘fires’
  • 6. Some proto-oncogenes Weinberg, Sci Am 275-3, 1996, 32-40
    • Receptor
      • PDGF: platelet-derived growth factor
        • glioma, a brain cancer
      • erbB: EGF receptor
        • glioblastoma, borstkanker
      • erbB2/HER-2/neu: EGF-R;
        • borstkanker, speekselklier, ovariumkanker
      • RET
        • schildklierkanker
    • Cytoplasmic, stimulatory
      • Ki-Ras
        • long-, ovarium-, pancreaskanker
    • Transcriptiefactoren
      • C-myc
        • leukemie, long-, borst-, maagkanker
    • Andere (apoptose!) Niet echt proto-oncogenen genoemd!
      • Bcl2; B - c ell l eukemia; blokkeert apoptose
      • Mdm2; m ouse d ouble m inute; sarcoma; p53 antagonist
    ======================================================
  • 7. Some tumor suppressor genes Weinberg, Sci Am 275-3, 1996, 32-40
    • APC
    • NF1
    • Rb
    • p53
    • WT1
    • BRCA1
    • BRCA2
    • VHL
    • Betrokken bij darm en maag kanker
    • Remt Ras; neurofibroma, leukemie
    • Retinoblastoma, oog-, blaas-, borstkanker
    • Stopt celdeling, stimuleert apoptose
    • Wilms tumor (nier)
    • Br east ca ncer: Borst en ovariumkanker
    • Als BRCA1; cytokinese?
    • Von Hippel Lindau: nierkanker
  • 8. Some tumor suppressor genes Weinberg, Sci Am 275-3, 1996, 32-40
    • APC
    • NF1
    • Rb
    • p53
    • WT1
    • BRCA1
    • BRCA2
    • VHL
    • Betrokken bij darm en maag kanker
    • Remt Ras; neurofibroma, leukemie
    • Retinoblastoma, oog-, blaas-, borstkanker
    • Stopt celdeling, stimuleert apoptose
    • Wilms tumor (nier)
    • Br east ca ncer: Borst en ovariumkanker
    • Als BRCA1; cytokinese?
    • Von Hippel Lindau: nierkanker
    DNA repair genen geen tumor suppressors noemen!
  • 9. The cell cycle Weinberg, Sci Am 275-3, 1996, 32-40
  • 10. The cell cycle Weinberg, Sci Am 275-3, 1996, 32-40
  • 11. The cell cycle Weinberg, Sci Am 275-3, 1996, 32-40
    • Cyclin associates with a cdk
      • Cyclin-dependent kinase
    • Cdk only active in complex with a cyclin
    Most cells are not cycling but in G 0 -stage
  • 12. The pRb switch Weinberg, Sci Am 275-3, 1996, 32-40 E2F-member
  • 13. The cell cycle Weinberg, Sci Am 275-3, 1996, 32-40
  • 14. The pRb switch Weinberg, Sci Am 275-3, 1996, 32-40 E2F-member
  • 15. Progression to cell division Weinberg, Sci Am 275-3, 1996, 32-40 mdm2 p21 p21 waf : see Vogelstein Proteins involved in DNA synthesis Liberated Transcription factors Active pRb protein complexed with inactive transcription factors (master brake) Transforming growth factor ß (an inhibitor) Cell division DNA synthesis Growth promoting signals issued vy neighboring cells
  • 16. Progression to cell division Weinberg, Sci Am 275-3, 1996, 32-40 mdm2 p21 p21 waf : see Vogelstein Proteins involved in DNA synthesis Liberated Transcription factors Active pRb protein complexed with inactive transcription factors (master brake) Transforming growth factor ß (an inhibitor) Cell division DNA synthesis Growth promoting signals issued vy neighboring cells
  • 17. The Ink4 locus Kim & Sharpless, 2006, Cell 127, 265-275
    • ARF: alternative reading frame
    • All 3 members inhibit progression of the cell cycle
    • Tumor suppressors
    • Ink4 is an E2F target gene
      • Feedback mechanism
    Inserted 4-12-07 http://www.mtmlabs.com/cda/science_technology/ p16supink4a/sup/content-121885.html
  • 18. Effect of activating c-myc (from Alberts et al. 2002)
  • 19. Effect of activating c-myc (from Alberts et al. 2002)
  • 20. Aberrant chromosomes: aneuploidy Weinberg, Sci Am 275-3, 1996, 32-40
    • DNA repair defect
    • Normal reaction:
      • Apoptosis
      • Senescence
        • Telomeres
    Karyotype ============