1. CANCER Definition Abnormal growth of cells that invade tissues and spread to other sites. Cell Regulation Normal Mitosis Reproduction occurs only when instructions are given to do so by other cells in their vicinity. Cancerous Mitosis Usual controls on proliferation are lost and cells follow their own internal agenda for reproduction.

2. CANCER Types of Tumors Benign (Noncancerous). Encapsulated with normal tissue. Non-spreading Malignant (Cancerous). Non-encapsulated. Metastasis Spread of a cancer from the original tumor to other parts of the body by means of tiny clumps of cells transported by the blood or lymph

6. ANGIOGENESIS

8. CELL DIVISION CONTROL External Regulators Cell Contact Signaling protein in the cell membrane of adjacent cell interacts with receptor protein on another cells membrane.

9. Signal Cell CELL CONTACT Receptor Cell Signal Protein Receptor Protein

11. CELL DIVISION CONTROL External Regulators Growth Hormones Signal molecules secreted by endocrine glands that bind to cell-surface or DNA receptors.

12. GROWTH HORMONE Growth Hormone

13. CELL DIVISION CONTROL External Regulators Growth Factors Signal proteins secreted by neighboring cells bind to cell-surface receptors.

14. GROWTH FACTORS Signaling Cell Receptor Cell Signal Molecule Receptor Protein

16. Fig. 25.6

17. CELL DIVISION CONTROL Internal Regulators Chemical Regulators (Proto-oncogenes) Kinases Proteins necessary for utilization of ATP during cell division. Cyclins Proteins that bind to kinases (cyclin- dependant-kinase complex) to stimulate their activation.

19. CELL DIVISION CONTROL Internal Regulators Chemical Regulators (Tumor Suppressor) p21 Protein Cdk inhibitor blocking cell division if DNA is damaged. p53 Protein Monitors DNA integrity Stimulates p21 production Stimulates repair enzymes Activates apoptosis

22. CELL DIVISION CONTROL Physical Regulators Telomere Structure Telomeres are a sequence of repetitive bases at the ends of linear chromosomes that prevent adjacent chromosomes from attaching to each other. Human Telomere Sequence (2000 repeats) 5'...TTAGGG TTAGGG TTAGGG TTAGGG TTAGGG TTAGGG..3‘ 3'...AATCCC AATCCC AATCCC AATCCC AATCCC AATCCC…5' Function They are crucial to maintaining chromosome stability

23. TELOMERES

24. TELOMERE Control Mechanism Process During each round of DNA replication, a section of the telomere base sequence is shaved off.

26. TELOMERE Control Mechanism Reason (DNA Replication) 1) DNA polymerase can only work in the 5’ to 3’ direction. 2) One strand is synthesized continuously and the other strand is synthesized in Okazaki fragments. 3) As the DNA polymerase reaches the end of the chromosome, there is not enough DNA template to synthesize more Okazaki fragments. 4) The 5’ end of each newly synthesized strand is cut short by 100 base pairs.

28. TELOMERE Control Mechanism Result Replicative Senescence.Cells removed from a newborn infant and placed in culture will go on to divide almost 100 times..Cells cultured from a 77 year old would only divide a couple of dozen times before they ceased dividing and die out.

29. CELL DIVISION CONTROL Genetic Regulators Proto-oncogenes Encourage cell growth and division

31. CELL DIVISION CONTROL Genetic Regulators Tumor Suppressor Genes Inhibit cell growth and division

33. MITOTIC DECISION MAKING PROCESS Step 1: Receiving Signal to Divide Activation Growth factors connect to cell membrane receptors Mutations Increased number of receptors Increased number of growth factors Therapies Bind proteins associated with receptors e.g. Herceptin (Monoclonal Antibody). Binds to HER-2 Receptor

34. Fig. 25.6

38. MITOTIC DECISION MAKING PROCESS Step 2: Passing the Signal via a Relay Switch Activation Ras protein changes shape to initiate relay signal by activating Tyrosine Kinase Mutations Continual relay signal Therapies None

39. Fig. 25.6

42. MITOTIC DECISION MAKING PROCESS Step 3: Amplifying the Signal Activation Tyrosine kinase activates other kinases in a relay signal cascade. Mutations Kinases continually activated Therapies Drug attaches to kinase to inactivate eg. Gleevac

43. Fig. 25.6

45. RAS

47. MITOTIC DECISION MAKING PROCESS Step 4: Releasing the Brake Activation Tumor-suppressor protein (eg. Rb) is inhibited allowing proto-oncogene protein (eg. E2F) to transcribe. Mutation Permanent inactivation of tumor- suppressor protein. Therapies Inactivation of proto-oncogene protein

48. Fig. 25.6

49. Fig. 25.5

52. MITOTIC DECISION MAKING PROCESS Step 5: Checking That Everything Is Ready Activation G 1 Checkpoint.Tumor-suppressor protein p53 released to check for damage. Environmental conditions checked. Cell growth checked

53. Fig. 5.1b

54. MITOTIC DECISION MAKING PROCESS Step 5: Checking That Everything Is Ready Activation G 2 Checkpoint. DNA replication checked. Environmental conditions checked. Cell growth checked. Damaged DNA checked

55. Fig. 5.1b

56. MITOTIC DECISION MAKING PROCESS Step 5: Checking That Everything Is Ready Activation M Checkpoint. Attachment of spindle fibers checked

57. Fig. 5.1b

58. MITOTIC DECISION MAKING PROCESS Step 5: Checking That Everything Is Ready Mutations With damaged p53, DNA is not repaired and goes through replication. Therapies Mutant Adenovirus destroys cells without active p53

61. MITOTIC DECISION MAKING PROCESS Step 6: Guarding Against Immortality Activation 1) Tumor-suppressor protein inhibits enzyme telomerase to allow reduction of telomeres. 2) Apoptosis results with the release of proteins to cause cell suicide Mutation 1) Inactivation of telomerase inhibitor allowing unlimited mitosis. 2) Inactivation of p53 to stop apoptosis Therapies 1) Inactivate telomerase 2) Radiation to cause DNA damage

64. Fig. 5.2