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

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

5 Ras participates in GFR signaling relays Ras

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

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

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

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

10 Fig. 2-7 The Cell Cycle

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

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

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

14 Fig Control Points in the Cell Cycle

15 Cell Death & Its Regulation Fig 1-19

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

17 Cell Death Is a Normal Component of Development

18 Fig 2-13 Early Apoptosis

19 Fig 2-13 Mid-Apoptosis

20 Fig 2-13 Late-Apoptosis

21 Photomicrographs of Apoptosis

22 Fig Apoptosis is triggered by activation of caspase (protease) cascades

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

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

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 Fig 2-15: Common Types of Induced DNA Damage

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

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

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

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

33 Fig Immune Reactions are Initiated in Response to Cancer Cells

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

35 Hallmarks of Cancer Hanahan and Weinberg 2000

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

37 Art of the Week

38 How to wage a war? Models!!

39 What makes a good cancer model?

40 Basic Research vs Applied Research

41 Commonly Used Cancer Research Models

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

43 Validation Bolstered by Whole Organism Genome Projects

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

45 THURS 2/5: Models and Angiogenesis Ch 3