Cancer and the Cell Cycle

1. Cancer and the Cell Cycle Chapter 2

2. Cancer is a complication of being a multiple-cell organism. The price we pay for being multicellular

3. What causes cancer? • Cancer cells are abnormal cells that arise from the body’s normal tissue through mutations. • Mutated genes that cause cancer are called oncogenes. • It is thought that several mutations need to occur to give rise to cancer • Cells that are old or not functioning properly normally self destruct and are replaced by new cells. • However, cancerous cells do not self destruct and continue to divide rapidly producing millions of new cancerous cells.

4. Cancer Causing Agents • Ionizing radiation • Chemicalsin the envionment • Virus infection • http://www.nih.gov/news/pr/jan2005/niehs-31.htm • Hereditary predisposition – Some families are more susceptible to getting certain cancers. Remember you can’t inherit cancer its just that you maybe more susceptible to getting it.

5. Central Points • Cancer involves uncontrolled cell division • Mutations in certain types of genes such as proto-onco genes and tumor supressor genes may lead to cancer. When genes are mutated and become cancer causing they are known as oncogenes. • Cancer is a disease that involves problems in the control of the cell cycle. • Breast, colon, and lung cancer are common types of cancer.

6. Benign or malignant? • Benign tumours do not spread from their site of origin, but can crowd out (squash) surrounding cells. • Malignant tumours can spread from the original site and cause secondary tumors. This is called metastasis. They interfere with neighbouring cells and can block blood vessels, the gut, glands, lungs etc. Why are secondary tumours so bad? • Both types of tumour can tire the body out as they both need a huge amount of nutrients to sustain the rapid growth and division of the cells.

7. Central Points • Cancer cells are abnormal cells that arise from the body’s normal tissue. • Environmental causes of cancer are being studied. Lawsuits have addressed smoking as a cause of cancer for example.

8. Are malignant tumors monoclonal in origin? That is derived from a single ancestral cell that underwent conversion from a normal cell to a cancerous state? Or are malignant tumors polyoclonal in origin that is many individual cells become cancerous and the resulting tumor represents the descendents of these original cells.

9. Monoclonal or polyclonal

10. Cancer Cells

11. Animation: How Cells Reproduce Cancer video HHMI video

12. How Is Genetics Involved? • Two classes of genes: Oncogenes and tumor suppressor genes • Proto-oncogenes: control cell division • Tumor suppressor genes turn off cell division • Mutated alleles, oncogenes, and tumor suppressor genes cause cells to divide uncontrollably

13. Mutations in Tumor Suppressor Genes Tumor suppressor genes Normal genes (regulate cell growth) Tumor suppressor genes Active oncogene 1st mutation (susceptible carrier) No brakes! 2nd mutation or loss (leads to cancer) No brakes! Active oncogene

14. Cancer-Causing Mutations • Exposure to environmental agents, virus, or lifestyle changes may cause a mutation • Certain virus infections can transform the cell • Human papillomavirus (HPV): Viral proteins interact with cell proteins, cause cervical cancer • Mistakes in DNA replication also cause mutations

15. G2/M checkpoint 4 Cell division 3 DNA repair 1 Mitosis G2 Cell grows, doubles in size G1 S Chromosome duplication 2 G1/S checkpoint

16. Regulation of Cell Cycle • G1/S checkpoint • G2/M checkpoint • Tumor suppressor genes and proto-oncogenes control these checkpoints • Tumor suppressor genes turn off or decrease rate of cell division • Proto-oncogenes turn on or increase rate

17. Signal Transduction • In normal cells, signals from outside cell can • Activate tumor suppressor genes (turning off cell division) or • Activate proto-oncogenes (turning  on  cell division) • Signals can be proteins, hormones, or nerve signals • May include steroids, pollutants, and other molecules

18. Process of Signal Transduction • Signal binds to a receptor in plasma membrane • Binding sets off series of interactions inside cell • Signal molecule may remain outside cell • Binding of signal changes shape of receptor and allows it to transmit signal to other proteins • May alter gene expression

19. Signal molecule Signal–receptor binding Cellular response Protein molecules Changes in gene expression Outside cell Receptor Plasma membrane Cytoplasm Nucleus

20. Ras Signaling • This is a detailed view of Ras interactions in pathways leading to: • cell proliferation • cell survival • differentiation • cell cycle control • cell motility • tumorigenesis

21. Produces RAS protein that: Attaches to inside of plasma membrane Is part of a pathway that turns on cell division Is signaled by growth factors from outside the cell Changes shape and switches on when activated Transfers signal to another protein in pathway Changes shape again after signal transmitted, switches off (inactive) Proto-OncogeneRAS (1)

22. Proto-Oncogene RAS (2) RAS mutations in many types of cancer, including colon, lung, pancreatic, and stomach cancer Mutant RAS stuck “on” and produces uncontrolled cell division

23. Cancer Genes on other Chromosomes

24. Environmental Factors and Populations • Determine types of cancer populations may develop • Many forms of cancer related to: • Physical surroundings • Personal behavior • Or both • At least 50% of all cancer can be attributed to some type of environmental factor

25. Spotlight on Ethics: HeLa Cell Line (1) • In 1951, cervical cells removed from Henrietta Lacks during biopsy • She died from cervical cancer • Cells maintained in vitro (in the lab) and used for worldwide scientific study • HeLa cells immortal because they can divide an unlimited number of times in a laboratory

26. Spotlight on Ethics: HeLa Cell Line (2) • Originally grown without Lacks’ knowledge or permission and later sold to medical schools • Have been used for commercial products: HPV vaccine