1. Cancer and Gene Regulation Chapter 18, Section 5

2. I. Cell Cycle is controlled by genes A. Many genes make proteins that regulate when a cell grows. (what we learned, what really happens)what we learnedwhat really happens ~examples of proteins – growth factors, cell receptors for growth factors, transcription factors B. Mutations to any gene involved in the cell cycle can cause cancer ~Causes of mutations include 1. spontaneous during DNA replication 2. chemicals from environment, x-rays, viruses

3. II. Gene types that cause cancer A. Proto-oncogene – normal gene that codes for proteins that control normal cell growth and division oncogene – cancer-causing gene; abnormal cell cycle mutates and becomes an

4. Example – Ras gene Oncogenes are PERMANENTLY ON ! This means that proteins that start cell division are ALWAYS BEING MADE ACTIVE. This is like pressing the gas pedal to its maximum ALL THE TIME. Found in 30% of all tested cancer cells.

5. B. Tumor Suppressor genes – normal genes that help prevent uncontrolled cell growth by 1. Making proteins that initiate repair of damaged DNA 2. Stopping over-damaged cells from dividing and initiating apoptosis -when these genes are turned on they functions normally

6. Example – p53 gene, aka Guardian of the Genome Example Cell divides with DNA damage Cell stopped from dividing Mutation in tumor suppressor gene turns the gene OFF, allowing all cells, normal and damaged, to divide. This is like taking the brake pedal away…thus you never stop! *Found in 50% of all tested cancer cells

7. III. Predispositions to Cancer A. It takes multiple mutations (~6 or more) within cell cycle regulation genes for cancer to occur. cancer incidence as you in age

8. Multiple mutations in colorectal cancer

9. B. You may inherit mutations (from egg or sperm) that increase your chances, but it’s not a guarantee of cancer. i.e. breast cancer (5-10%), colorectal cancer (15%), pancreatic cancer (10%) ***Recall that genes are made up of TWO alleles, one from mom and one from dad. If one allele is functioning normally and is dominant over the mutated (recessive) allele, you are fine. p53 = A a where a is mutant, p53 gene is fine and will produce a normal protein. But, if the dominant/normal allele acquires a mutation, then that whole gene is mutated and will not properly function. p53 = a a, the gene is defective and will not produce a protein OR will produce a nonfunctional protein.

10. IV. Viruses and Cancer A. Viruses are linked to ~15% of all cancers. They insert their DNA into yours, interfering with gene regulation B. Examples – HPV (human papilloma virus) and cervical cancer, Epstein-Barr virus (causes mono) linked to lymphomas and nasopharyngeal cancers

11. Cell cycle controlled by cyclins and cyclin- dependent kinases (CDKs) Slide 2

12. Some (not all) of the proteins (made by your genes) that control the cell cycle Slide 2