2. Cancer- A Deeper Look (Part 4) Ms. Gaynor Honors Genetics

3. Genes and Cancer Proto-oncogenes – Genes that create proteins that normally activates cell division growth factor genes become oncogenes (cancer-causing) when mutated Tumor-suppressor genes – normally inhibits (turns “off”) cell division – if switched “OFF” can cause cancer – example: p53 gene

4. Tumor-Suppressor Genes – Mutations that inactivate tumor suppressor genes Have similar effects as oncogenes Tumor-suppressor gene Mutated tumor-suppressor gene Normal growth- inhibiting protein Cell division under control Defective, nonfunctioning protein Cell division not under control

5. What causes cancer? Cancer starts with a mutation of a normal gene. 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 (APOPTOSIS) and are replaced by new cells. Cancerous cells do not self destruct and continue to divide rapidly producing millions of new cancerous cells.

6. Cancer cells are “hungry”… Angiogenesis – is the recruitment of blood vessels from the network of neighbouring vessels. Without blood and the nutrients it carries, a tumor would be unable to continue growing.

7. A factor which brings about a mutation in DNA is called a mutagen. A mutagen is mutagenic. Any agent that causes cancer is called a carcinogen and is described as carcinogenic. Some mutagens are carcinogenic.

8. Some Carcinogens Radiation – X Rays, UV light Chemicals – tar from cigarettes Virus infection – papilloma virus can be responsible for cervical cancer. 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.

9. Cancer & Cell Growth Cancer = failure of cell division control What control is lost? –lose checkpoint “stops” Gene p53 plays a key role in G 1 checkpoint p53 protein STOPS cell division if it detects damaged DNA –Options: stimulates repair enzymes to fix DNA forces cell into G 0 resting stage keeps cell in G 1 arrest  causes apoptosis of damaged cell 50% cancers have a mutation in p53 gene p53 is the Cell Cycle Enforcer

10. DNA damage is caused by heat, radiation, or chemicals. p53 allows cells with repaired DNA to divide. Step 1 DNA damage is caused by heat, radiation, or chemicals. Step 1 Step 2 Damaged cells continue to divide. If other damage accumulates, the cell can turn cancerous. Step 3 p53 triggers the destruction of cells damaged beyond repair. ABNORMAL p53 NORMAL p53 abnormal p53 protein cancer cell Step 3 The p53 protein fails to stop cell division and repair DNA. Cell divides without repair to damaged DNA. Cell division stops, and p53 triggers enzymes to repair damaged region. Step 2 DNA repair enzyme p53 protein p53 protein p53 — master regulator gene

11. http://www.hhmi.org/biointeractive/media/p53-lg.mov

12. Development of Cancer Cancer develops when mutations accumulate: – unlimited growth turn on growth promoter genes – ignore checkpoints turn off tumor suppressor genes (p53) – escape apoptosis turn off suicide genes – immortality = unlimited divisions turn on chromosome maintenance genes – promotes blood vessel growth turn on blood vessel growth genes – overcome anchor & density dependence turn off touch-sensor gene It’s like an out-of-control car with many systems failing!

13. What causes these mutations? Mutations in cells can be triggered by  UV radiation  chemical exposure  radiation exposure  heat  cigarette smoke  pollution  age  genetics

14. – Colon cancer Develops in a stepwise fashion Colon wall Cellular changes: DNA changes: 1 Increased cell division Oncogene activated 2 Growth of polyp Tumor-suppressor gene inactivated 3 Growth of malignant tumor (carcinoma) Second tumor- suppressor gene inactivated Figure 11.18A

15. – Cancer in the United States

16. Avoiding carcinogens can reduce the risk of cancer – Reducing exposure to carcinogens (which induce cancer-causing mutations) Making other lifestyle choices can help reduce cancer risk What’s the CONNECTION to me?