The Cell Cycle and Cancer

1. The Cell Cycle and Cancer

2. Cell signaling: chemical communication between cells. A chemical signal to a receptor on the outside of a cell may trigger a second chemical response inside the cell. This may be the first step of an entire chemical cascade of chemical signals that trigger actions in the cell. Click on above to go to animation

3. Cancer • Normal cell division: • Controlled by cell cycle checkpoints • CHECKPOINTS – critical control points that determine if a cell will move to the next portion of the cell cycle. • Cancerous cell division: • Ignores the cell cycle checkpoints • Caused by DNA mutations • Cells grow and divide out of control • Cancerous cells do not perform designated purpose. • Crowd out normal cells that do perform designated purpose.

4. The Stages of the Cell Cycle 1. Click on picture for cell cycle animation – will go to www.cancerquest.org) 2. Use alt-tab keys to go between website and power point presentation. 3. Click on blank space to proceed to next slide.)

5. 1.Before a cell divides, the DNA is checked to make sure it has replicated correctly. (If DNA does not copy itself correctly, a gene mutation occurs. There are several factors that regulate the cell cycle and assure a cell divides correctly. DNA replication animation:click on DNA picture

7. Cell Cycle Checkpoints • G1/S • Monitors cell size and for DNA damage • G2/M • Replication complete, DNA damage? • M • Spindle fibers connected, etc.? • G0 • Does body require more of my type of cell?

8. Control of cellular division • Genes code for proteins that either stimulate cell growth or suppress it. • Cyclins: proteins that control phases of the cell cycle. • Examples: • S-cycline stimulates DNA replication • M-cycline helps trigger mitosis • Growth factors supervise progress through the cycle. • Sometimes trigger genes to make cyclins. • Sometimes block cyclins • Proto-oncogenes: genes involved in growth stimulation • Mutation here can produce an “onco-gene” which triggers uncontrolled growth. GAS PEDAL • Tumor suppressor genes: inhibit growth and division • Mutation here = loss of inhibition BRAKE • Cells divide out of control without normal functioning suppressor gene • or suppress cell growth and division.

9. Example of a tumor suppressor gene: • p53 gene codes for apoptosis: (Programmed cell death)

10. 2. Chemical Signals tell a cell when to start and stop dividing. (Target cells animation: click on go sign)

11. Control of cell division continued:Density Dependent Inhibition: Normal cells cease dividing once critical cell density is reached. Cancer cells do not possess this trait.

12. Neighboring cells communicate with dividing cells to regulate growth. (Normal contact inhibition animation: click on petri dish)

13. Anchorage dependence: proteins located in plasma membrane indicate attachment to neighboring cells/tissue

14. Carcinogens: 1. radiation 2. smoking 3. Pollutants 4. chemicals 5. viruses 6. Heredity DNA mutations disrupt the cell cycle.

15. What causes the mutations that lead to cancer? • Viruses: HPV --> cervical cancer • Bacteria: H. pylori --> gastric cancer (bacteria usually not a known carcinogen) • Chemicals --> lung cancer • UV radiation --> skin cancer • What do these agents have in common?

16. Multistep Process: Cancer results from “multiple hits” • Cancer requires mutation of multiple genes • Age relationship: • Cancer rate increases dramatically with age. • Delay between carcinogen exposure and onset • 5-8 year delay between carcinogen exposure (Hiroshima and Nagasaki) and onset of leukemia • 15 year delay between tuberculosis X-ray treatment and onset of breast cancer

17. Age and Cancer • Note log scale for incidence rate

18. Tumors in Liver Tumor in Colon Cancer is a disease of the cell cycle. Some of the body’s cells divide uncontrollably and tumors form.

19. While normal cells will stop dividing if there is a mutation in the DNA, cancer cells will continue to divide with mutation.

20. Due to DNA mutations, cancer cells ignore the chemical signals that start and stop the cell cycle. They don’t communicate with neighboring cells and continue to grow and form tumors. 2 animations of cancer cells dividing: click on picture

21. Normal Cell Division DNA is replicated properly. 2. Chemical checkpoints signal start and stop of the cell cycle. 3. Cells communicate with each other so they don’t become overcrowded. Cancer Cells Mutations occur in the DNA 2. Ignores normal checkpoints = excessive division 3. Unusual # of chromosomes Loss of attachment and other control mechanisms Immortality Extensive angiogenesis SUMMARY

22. Normal and Cancer Karyotypes • (a) is a normal cell, (b) is a cancer cell

23. Benign or malignant? • Benign tumors do not spread from their site of origin, but can crowd out surrounding cells. • Malignant tumors can spread from the original site and cause secondary tumors. This is called metastasis.

24. Metastasis: cells travel through blood vessels or lymph to other areas of the body and grow there. This is what makes tumors so lethal. • interfere with normal functioning of other tissues vital to survival. . Pathways of cancer: cell signaling

25. Treating Cancers Cancer treatments include drugs that can stop cancer cells from dividing. Chemotherapy: Radiation: Surgery: Other medications designed to assist the body in preventing cancerous cell division.

26. Cancer therapies targets • Classic cancer therapies target rapidly dividing cells • Radiation • Chemotherapy • Side effects • Hair loss • Weakened immune system • Digestive tract issues

27. Cancer therapies target • immune system may not target tumor cells because they appear to be “self” • Some therapies activate one's immune system against a cancer

28. Cancer therapies target • Modern, therapies attack specific proteins that are abnormally expressed in a tumor • Block over-expressed growth factor receptors --> Herceptin • Target cancer cells so less side effects.