1. 1 Dr. Karen Schmeichel February 3, 2009 BIO 290 Special Topics in Biology: Cancer Biology Lecture #7 Finishing “Profiling” & “Models Of Cancer”

2. 2 Business Items: Feb 12 7 PM Darwin Day Lecture Sign Thank You Card Second Journal Entry due 2/10/09 A note on WDIC sheets

3. 3 Objectives: Continue with a discussion of growth factor mediated activation of the cell cycle Discuss molecular pathways regulating apoptosis Understand that immune system is an important surveillance system Consider how to wage “War on Cancer”: the best model

4. 4 Profile of a Cancer Cell: Proliferation Growth Factor & Cell cycle Apoptosis & Cell Survival Genetic Instability Tumor immunology

5. 5 Ras participates in GFR signaling relays Ras

6. 6 Ras Signaling Ends with a MAP Kinase Cascade From Lodish et al. Molecular Cell Biology

7. 7 In cancer cells Ras is mutated such that it is always on Activated Ras

8. 8 Fig 2-6 In some cancer cells, GFRs can be activated in the absence of GF!

9. 9 How do Growth Factors and Their Signaling Cascades Stimulate Cell Growth? Ties to the Cell Cycle

10. 10 Fig. 2-7 The Cell Cycle

11. 11 Fig. 2-8 Cell cycle: Driven By formation CDK-Cyclin complexes

12. 12 Fig. 2-9 Mitotic CDK-Cyclin activation also requires a series phosphorylation/dephosphorylation events

13. 13 Fig. 2-10: How Growth Factors Activate Cell Cycle

14. 14 Fig. 2-11 Control Points in the Cell Cycle

15. 15 Cell Death & Its Regulation Fig 1-19

16. 16 Apoptosis: A Normal Regulated Cellular Suicide Process Used to Clear Unneeded or Defective Cells

17. 17 Cell Death Is a Normal Component of Development

18. 18 Fig 2-13 Early Apoptosis

19. 19 Fig 2-13 Mid-Apoptosis

20. 20 Fig 2-13 Late-Apoptosis

21. 21 Photomicrographs of Apoptosis

22. 22 Fig. 2-13 Apoptosis is triggered by activation of caspase (protease) cascades

23. 23 Why Aren’t Cancer Cells Cleared By Apoptosis? Ex., p53 mutations

24. 24 Profile of a Cancer Cell: Proliferation Growth Factor & Cell cycle Apoptosis & Cell Survival Genetic Instability Tumor immunology

25. 25 Mutations: Changes in DNA base sequence that arise either spontaneously or as a result of exposure to mutation-causing agents in the environment.

26. 26 Fig 2-15: Common Types of Induced DNA Damage

27. 27 Fig 2-17: Errors Incurred During Routine DNA Replication

28. 28 Fig 2-16: Normal Cells Have DNA Repair Mechanisms

29. From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Fig 2-18: Double strand breaks lead to gross chromosomal defects

30. 30 Fig. 2-19: Genomic Instability via Larger Chromosomal Rearrangements

31. From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Fig. 2-19: Are DNA Mutations sufficient to induce cancer? (transfections a la R. Weinberg)

32. 32 Profile of a Cancer Cell: Proliferation Growth Factor & Cell cycle Apoptosis & Cell Survival Genetic Instability Tumor immunology

33. 33 Fig. 2.21 Immune Reactions are Initiated in Response to Cancer Cells

34. 34 Profile of a Cancer Cell: Proliferation Growth Factor & Cell cycle Apoptosis & Cell Survival Genetic Instability Tumor immunology AND MANY MORE…..

35. 35 Hallmarks of Cancer Hanahan and Weinberg 2000

36. 36 Nixon’s “War on Cancer” State of the Union 1971

37. 37 Art of the Week

38. 38 How to wage a war? Models!!

39. 39 What makes a good cancer model?

40. 40 Basic Research vs Applied Research

41. 41 Commonly Used Cancer Research Models

42. 42 Evolution Validates The Use of Non-Human Models in Human Disease Research

43. 43 Validation Bolstered by Whole Organism Genome Projects

44. 44 1.Why use the model system? 2.What questions can be studied? 3.Basic or Applied? 4.Which is the “Best” model?

45. 45 THURS 2/5: Models and Angiogenesis Ch 3