THE CELL CYCLE AND CANCER

1. THE CELL CYCLE AND CANCER

2. Control of the Cell cycle • Control of the cell cycle

3. Cell division and cancer Which karyotype is the bladder cancer cell?

4. This representative karyotype from a human prostate cancer cell line before injection into nude mice shows all human chromosomes with characteristic marker chromosomes

5. OK…what tells a cell when to divide (or, indeed, when NOT to divide)?

6. Cell cycle controls

7. Cell Cycle Control Leland Hartwell Isolated > 100 genes (in yeast cells) directly involved in control of the cell cycle (CDC genes) Introduced the concept of ‘Checkpoints’: where the cell cycle stops to check if DNA has been perfectly duplicated, cell size is correct, etc etc…

8. Cell cycle control Sir Paul Nurse Used another yeastcell (Saccharomyces) to identify the CDC2 gene (and subsequently the equivalent gene in humans, CDK1), which was THE rate-limiting step controlling onset of S, transition from G1 to S and from G2 to M phase of the cell cycle

9. Cell Cycle Control Tim Hunt Used sea urchins to identify control proteins which were formed and degraded throughout the cell cycle (cyclins) and bind with CDK molecules, regulating CDK activity and selecting proteins to be phosphorylated

12. OK…what tells a cell when to divide (or, indeed, when NOT to divide)? • Let's get some help from the NOBEL organisation... • and how about some help from Harvard? • Animation

13. What is the relationship between the cell cycle and cancer? What roles do CDK and cyclin play in the development of cancer? Cancer & The Cell Cycle

14. Cell cycle regulators • Cyclins and kinase proteins regulate the timing of the cell cycle in eukaryotic cells • They are sometimes called internal regulators – proteins that respond to events inside the cell • They include growth factors • They direct cells to speed up or slow down the cell cycle • They prevent excessive cell growth and prevent tissues from disrupting each other

15. What’s the link between control of the cell cycle and cancer? • In cancer, defective cell cycle control means that parts of chromosomes are lost, rearranged or unequally distributed between daughter cells • Genes for CDK and cyclins can function as oncogenes • Increased levels of CDK and cyclins are often identified in human cancer cells (e.g. skin, breast)

16. ‘Faulty’ cell division: oncogenes An oncogene is a mutated gene that contributes to the development of a cancer. In their normal, unmutated state, oncogenes are called proto-oncogenes, and they play roles in the regulation of cell division

17. Development of a Tumor Angiogenesis from the Howard Hughes Medical Institute

18. An introduction to the biology of cancer • Cold Harbour website

19. How does cancer compare to other causes of death in the developed world? • What percentage of all deaths is attributed to cancer?

20. US mortality 2010

21. US Mortality, 2004 No. of deaths % of all deaths Rank Cause of Death • 1. Heart Diseases 652,486 27.2 • 2. Cancer553,888 23.1 • 3. Cerebrovascular diseases 150,074 6.3 • 4. Chronic lower respiratory diseases 121,987 5.1 • 5. Accidents (Unintentional injuries) 112,012 4.7 • 6. Diabetes mellitus 73,138 3.1 • 7. Alzheimer disease 65,965 2.8 • 8. Influenza & pneumonia 59,664 2.5 • Nephritis 42,480 1.8 • 10. Septicemia 33,373 1.4 Source: US Mortality Public Use Data Tape 2004, National Center for Health Statistics, Centers for Disease Control and Prevention, 2006.

22. Who gets what type of cancer?

23. 2007 Estimated US Cancer Deaths* Men289,550 Women270,100 Lung & bronchus 31% Prostate 9% Colon & rectum 9% Pancreas 6% Leukemia 4% Liver & intrahepatic 4%bile duct Esophagus 4% Urinary bladder 3% Non-Hodgkin 3% lymphoma Kidney 3% All other sites 24% 26% Lung & bronchus 15% Breast 10% Colon & rectum 6% Pancreas 6% Ovary 4% Leukemia 3% Non-Hodgkin lymphoma 3% Uterine corpus 2% Brain/ONS 2% Liver & intrahepatic bile duct 23% All other sites ONS=Other nervous system. Source: American Cancer Society, 2007.

24. 2007 Estimated US Cancer Deaths* Men289,550 Women270,100 Lung & bronchus 31% Prostate 9% Colon & rectum 9% Pancreas 6% Leukemia 4% Liver & intrahepatic 4%bile duct Esophagus 4% Urinary bladder 3% Non-Hodgkin 3% lymphoma Kidney 3% All other sites 24% 26% Lung & bronchus 15% Breast 10% Colon & rectum 6% Pancreas 6% Ovary 4% Leukemia 3% Non-Hodgkin lymphoma 3% Uterine corpus 2% Brain/ONS 2% Liver & intrahepatic bile duct 23% All other sites ONS=Other nervous system. Source: American Cancer Society, 2007.

25. P53: a famous oncogene • p53 from Howard Hughes • p53 movie • cancer treatment using the common cold!

26. Key Statements from the WHO: • Tobacco use is the major preventable cause of cancer in the world. • Molecular genome research will reveal a tremendous amount of information on cancer but it is not clear how easy these discoveries will translate into actual lives saved and may well be restricted to rare cancers • Researchers will demonstrate that successful behavioral changes in tobacco, alcohol and diet will prevent far more cancers than the elimination of toxins such as industrial pollution, car exhaust and dioxins; .

27. More than genes • Tobacco, the case for primary prevention • Infection and cancer: intervention is key • Poverty, affluence and the global burden of cancer • The Western lifestyle and its health risks

28. Key Statements from the WHO: • The Pap smear for cervical cancer is the single best cancer screening procedure. • In 2000, the last year for which global data exists, some 400,000 women died from breast cancer, representing 1.6 per cent of ALL female deaths.

29. Discussion • Read your section and discuss it with your partner/group members. • Highlight the key points and be prepared to share them with the class.

30. The good news • Early detection and a healthy diet • (>1.1lbs of fruits/vegetables per day can lower your risk for cancers of the digestive tract by 25%).