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Why do normal cells divide? (8.1, 8.2) • • • • • Replacement Repair Growth Regeneration Formation of sperm and egg Cell Division (mitosis) • All new cells arise from previous cells • Some cells reproduce once in a lifetime – Example: neurons in the brain • Some reproduce every few days – Example: skin cells, embryo Cells contain DNA • Chromosomes – strands of DNA – Genes (~2% of DNA) – Chromosomes also contain proteins Before a cell can replicate, it must replicate its DNA – why? “Parent” cell “Daughter” cells The cell cycle (8.4) Tightly regulated! Many checkpoints that delay the cell cycle until cell is ready Mitosis is relatively fast “questions” the cell asks at each checkpoint • Do I really want to reproduce? • Was the DNA replicated? correctly? • Are the chromosomes moving into daughter cells correctly? • Are there enough growth factors? • Is the cell large enough to divide? • Have mistakes in the DNA been repaired? • Is the whole process moving at the right rate? Control of the cell cycle (8.4, 12.2) To GO (the “pedal”) A. Growth factors • Stimulate cells to grow • Example: growth hormone B. Growth factor receptors • allow the cell to respond to a growth factor • Example: GH receptor To SLOW! (the “brake”) Checkpoint proteins A. Tumor suppressors • prevent cell from continuing in cell cycle and send cell to apoptosis if necessary B. DNA repair proteins • • if DNA cannot be repaired, cell should undergo apoptosis Example: UV repair A leukemia cancer cell in apoptosis What happens if multiple types of control genes are mutated in a single cell? • Extra growth factor? • A growth factor receptor that is always on or too many copies? • Failure of a tumor suppressor? • Failure of DNA to repair? Cancer genes Cancer is a genetic disease = genes are mutated Genes that encode normal cell cycle control proteins are called proto-oncogenes oncogene = mutated proto-oncogene, can lead to cancer cell Proto-oncogene (normal) -------- oncogene (cancer causing) • mutation Cancer is a multi-hit disease More than one mutation in a single cell required Characteristics of cancer cells (8.5 and 12.2)? How are cancer cells different from normal cells 1. Immortal (unless killed) cancer cells keep dividing 2. Loss of contact inhibition results in tumor formation Contact inhibition 3. Changes in cell membrane NORMAL SKIN CELLS ROUNDED CELL MEMBRANES 4. Angiogenesis – tumor gets its own blood supply 5. Enlarged nuclei, abnormal chromosomes Translocation in CML (remember the cytogenetics lab?) Enlarged nuclei in color cancer cells 6. Undifferentiated cells don’t resemble normal cells and grow very fast 7. Escape apoptosis 8. May metastasize Carcinogenesis tumorigenesis metastasis (12.2) a. Mutation in a single cell b. Second mutation occurs c. Third mutation in one cell + other mutations Note: tumor formation d. Tumor cells invade surrounding tissue e. metastasis= cancer cells enter blood vessel Tumor types • Malignant = cancer cells invade surrounding tissues and break off • Benign tumor – Benign tumors are in a fibrous capsule Treatments for cancer (8.5) • Excision = Remove cancerous tissue by surgery Chemotherapy (drugs) • The use of chemicals to treat disease • stop cell growth in fast growing cells – What are normally fast growing cells? • Many come from plants Radiation – Destroys DNA of fast growing cells, shrinks tumors, has side effects Cancer vaccines • Human papilloma virus (HPV) causes genital warts • Over time, in SOME women, this leads to cervical cancer • 500,000 cases per year, the vaccine can prevent most of them • Gardasil is the name of the vaccine • Hepatitis vaccine protects against liver cancer Risk factors for cancer Genetics •some people inherit predispositions (cells have at least 1 mutation at birth) Age •the older you are the more time for multiple mutations to arise Smoking Diet •20 carcinogens in tobacco smoke •fat, meat Environment •chemicals, sunlight, X-rays Predisposition genes for cancer • inherit 2 alleles for each gene • Example: tumor supressor gene • Both alleles need to be mutated for cancer to occur • BUT, if a person inherits one mutated allele, then the risk of cancer increases Breast Cancer (pg 191) as an example of cancer predisposition genes • Breast cancer 2nd highest cause of cancer death in US women (~44,000 women and 400 men/ year) • BRCA1 gene 200,000/1600 diagnosed BRCA-1 gene encodes a tumor suppressor protein • If both inherited alleles are normal, 13 % chance of breast cancer • If one mutant allele is inherited, 30 – 80% chance of early breast cancer