1. Cancer A Disease Resulting from Uncontrolled Cell Growth

2. Due to lack of specialization, cancer cells have a different appearance than surrounding cells. Cancer cells have enlarged nuclei and may have extra chromosomes. They are genetically unstable and accumulate mutations. Normal cervical cells Precancerous cervical cells Cancerous cervical cells Properties of Cancer Cells

3. Non-cancerous cells form sheets. Cancer cells grow into tumors, showing a lack of contact inhibition. Cancer cells do not respond to signals from Growth factors—stimulate or inhibit cell division Apoptosis factors—promote death of cells with damaged DNA Apoptosis factors—promote death of cells with damaged DNA Properties of Cancer Cells

4. Cancer cells divide more frequently and for an unlimited number of times due to an abundance of telomerase, an enzyme that repairs the ends of chromosomes Cancer cells show metastasis, an invasion of other tissues Angiogenesis: cancerous tumors grow new blood vessels for delivery of nutrients and oxygen Properties of Cancer Cells

5. Cancer is the result of multiple mutations causing uncontrolled growth

6. Normal Cell Growth Involves the Cell Cycle with Mitosis G1 cytoplasm doubles S chromosomes replicate G2 assembly of components for division cytokinesis P M A T Mitosis Mitosis includes P = prophase M = metaphase M = metaphase A = anaphase T = telophase Interphase includes G1 = growth phase 1 S = synthesis phase S = synthesis phase G2 = growth phase 2 Interphase

7. Mitosis = Chromosomal Division Leading to Genetically Identical Nuclei Chromosomes align individually at the cell equator so each daughter cell receives one copy of each chromosome

8. Control of the Cell Cycle Mechanisms for controlling progress through the cell cycle Mechanisms for controlling progress through the cell cycle Extracellular Signals Extracellular Signals Control the timing of cell division Control the timing of cell division Transitions Transitions Orderly progression from one stage of cell cycle to another Orderly progression from one stage of cell cycle to another Depend on the production of proteins called cyclins Depend on the production of proteins called cyclins Checkpoints Checkpoints Delay progression to next stage if cell must repair damage Delay progression to next stage if cell must repair damage

9. Control of the Cell Cycle Involves Activities at Transitions and Checkpoints G1 S G2 cytoplasm doubles chromosomes replicate assembly of components for division cytokinesis P M A T Mitosis G1  S Transition G2  M Checkpoint DNA Damage Checkpoint ApoptosisCheckpoint G2  M TransitionSpindleAssemblyCheckpoint G1  S Checkpoint S  G2 Transition Signals initiate self-destruction if DNA damage is severe

10. Extracellular Signals Activate Genes Controlling Cell Division Gene product inhibits cell division and promotes apoptosis Gene product stimulates cell division and prevents apoptosis

11. Mutations That Cause Cancer Gene Type Normal Function In Cancer Mutation Type Proto- Oncogene In response to extracellular or intracellular signals, promotes cell division and prevents apoptosis  Oncogene Promotes cell division in absence of signals Dominant Tumor Suppressor Gene Inhibits cell division and promotes apoptosis Active gene product no longer available to control cell division Recessive example Ras examples RB p53

12. Applying Your Knowledge Indicate whether each statement is TRUE or FALSE Cancer cells escape the normal controls on cell division.Cancer cells escape the normal controls on cell division. Oncogenes are recessive mutations.Oncogenes are recessive mutations. The growth of a cancer cell is stopped by contact with another cell.The growth of a cancer cell is stopped by contact with another cell. Cancer-causing mutations in tumor suppressor alleles inhibit cell division.Cancer-causing mutations in tumor suppressor alleles inhibit cell division. TRUE: Thumbs Up FALSE: Thumbs Down

13. Ras Proto-Oncogene In response to growth factor binding at receptor, the Ras gene product combines with GTP to promote cell division In cancer cells, the RAS gene product is locked into its GTP-binding shape and does not require a signal at the receptor in order to stimulate cell division

14. In Normal Cells, the Rb Gene Product Controls the G1  S Transition RB = product of Retinoblastoma gene, inhibits action of E2F until chemically modified due to buildup of CDK-cyclins (intracellular signals) In people who are heterozygous for a mutation in the RB gene (Rb + Rb - ), there is a tendency for the functional copy of the RB gene (Rb + ) to mutate to Rb -. Retinal cancer develops because growth of tumor cells is no longer controlled at the the G1  S transition. E2F = transcription factor required to activate genes for DNA synthesis

15. In Normal Cells, the p53 Gene Product Acts at the G1  S Checkpoint Preventing Entry Into S Phase If DNA Is Damaged p21 inhibits intracellular signals that would activate E2F p53 = transcription factor that causes p21 to be produced Cells with damaged DNA do not pass the G1  S checkpoint In cancer cells the mutated p53 gene product no longer stimulates p21 production. Cells will pass the G1  S checkpoint even when chromosomal damage exists.

16. In Normal Cells, the p53 Gene Product Stimulates Apoptosis If DNA Damage Cannot Be Repaired p53 gives an internal signal for apoptosis In cancer cells, a mutated p53 gene product no longer initiates self-destruction. Cells with damaged DNA can divide and more DNA damage can be accumulated. p53 is the most frequently mutated of all known cancer-causing genes, contributing to many types of cancer.

17. Applying Your Knowledge Which description best represents the Cancer-causing allele for Rb protein?Cancer-causing allele for Rb protein? Cancer-causing p53 mutation?Cancer-causing p53 mutation? Cancer-causing RAS allele?Cancer-causing RAS allele? Thumbs Up: Dominant Oncogenic Allele Thumbs Down: Recessive Tumor Suppressor Allele

18. Causes of Cancer HeredityHeredity –tendency to develop cancer can be inherited due to mutations in tumor suppressors –BRCA1 and RB are examples Environmental CarcinogensEnvironmental Carcinogens –agents that contribute to cancer development, often by causing mutations

19. Causes of Cancer Environmental CarcinogensEnvironmental Carcinogens –Radiation ultraviolet radiation in sunlightultraviolet radiation in sunlight nuclear radiationnuclear radiation –Organic chemicals found in tobacco smoketobacco smoke pollutantspollutants –Viruses hepatitis B virushepatitis B virus Epstein-Barr virusEpstein-Barr virus Human papilloma virusHuman papilloma virus HIVHIV

20. Cancer Prevention Protective BehaviorsProtective Behaviors –Avoid Carcinogens –Get regular screening tests –Get vaccinated Dietary HabitsDietary Habits –Avoid excess weight gain –Exclude foods that promote cancer– salt-cured or smoked foods, excess alcohol –Include protective foods with fiber, vitamins A and C, and cruciferous vegetables

21. Treatment of Cancer Traditional TherapiesTraditional Therapies –Surgery –Radiation –Chemotherapy restore immune function with bone marrow transplantsrestore immune function with bone marrow transplants Newer TherapiesNewer Therapies –Immunotherapy –p53 gene therapy Genetically-engineered adenovirus that can infect and kill p53-deficient cancer cellsGenetically-engineered adenovirus that can infect and kill p53-deficient cancer cells –Targeted therapy acting on specific molecules Herceptin blocks growth factor receptors on breast cancer cellsHerceptin blocks growth factor receptors on breast cancer cells Gleevec inhibits the action of a faulty tyrosine kinase related to uncontrolled bone marrow cell reproduction in Chronic Myelogenous LeukemiaGleevec inhibits the action of a faulty tyrosine kinase related to uncontrolled bone marrow cell reproduction in Chronic Myelogenous Leukemia