1. Control of cell division/Cancer

2. Figure 12.1 The functions of cell division Reproduction Growth and development Tissue repair

3. Figure 12.5 The cell cycle

4. Figure 12.4 Chromosome duplication and distribution during mitosis

5. Figure 12.5 The cell cycle

6. Figure 16.12 Origins of replication in eukaryotes

7. Figure 12.5 The cell cycle

9. Figure 12.6 The stages of mitotic cell division in an animal cell: G 2 phase; prophase; prometaphase

10. Figure 12.6 The stages of mitotic cell division in an animal cell: metaphase; anaphase; telophase and cytokinesis.

11. Cytokinesis in plants.

12. Cell Cycle control The interesting stuff! –How do cells “decide” whether and when to divide? –Checkpoints –What happens when cell cycle control is lost?

13. Figure 12.5 The cell cycle

14. Figure 12.14 Mechanical analogy for the cell cycle control system Figure 12.15 The G1 checkpoint

15. Cell and Organismal Biology 2009

16. Figure 12.13 Evidence for cytoplasmic chemical signals in cell cycle regulation

19. Figure 12.16 Molecular control of the cell cycle at the G 2 checkpoint MPF-Mitosis promoting factor

22. Figure 12.17 The effect of a growth factor on cell division Fetal Calf Serum Experiment Results

23. Figure 12.18 Density-dependent inhibition of cell division

26. Loss of control of the cell cycle: Cancer

27. Types of Cancer Epithelial cell tumors (Carcinoma) –Adenoma-benign –Adenocarcinoma-malignant glandular Connective tissue or muscle cell tumors (Sarcoma) –Chondroma-benign –Chondrosarcoma-malignant cartilage tumor Others –Leukemias and nervous system cancers

28. Progression of tumor size- Breast cancer doubling time is 100 days Mammogram: normal (left) and cancerous (right)

29. Cancers are progressive Epithelial cell tumor

30. Steps in the process of metastasis

31. Papanicolaou test “Pap smear” A. Normal cells- well differentiated B. Precancerous-abnormal differentiation C. Invasive carcinoma-undifferentiated

32. Cancer incidence as a function of age Colon cancer in women in England and Wales Suggests multiple mutations required to induce cancer

39. So how is cancer caused? Genes involved in cell cycle regulation are mutated

40. Genes controlling cell division that can cause cancer Oncogenes- these are mutated proto-oncogenes which push cells towards cell division (GF receptors, myc, ras etc) Tumor-suppressor genes-these are genes that stop cells from dividing (retinoblastoma, p53 APC etc)

41. Importance of Structure-an example P53 Mutated in 50% of all human cancers

42. Cell and Organismal Biology 2009

43. Figure 19.11 Genetic changes that can turn proto-oncogenes into oncogenes

45. Genes controlling cell division that can cause cancer Oncogenes- these are mutated proto-oncogenes which push cells towards cell division (GF receptors, myc, ras etc) –ras-mutated in 20-30% of all cancers –GF receptors-increased in number in many breast cancers –src kinase- mutated/affected in 2-5% of cancers Tumor-suppressor genes- these are genes that stop cells from dividing –P53-mutated in 50% of cancers –Rb-mutated in 40% of cancers

47. Genes controlling cell division that can cause cancer Oncogenes- these are mutated proto-oncogenes which push cells towards cell division (GF receptors, myc, ras etc) –ras-mutated in 20-30% of all cancers –GF receptors-increased in number in many breast cancers –src kinase- mutated/affected in 2-5% of cancers Tumor-suppressor genes- these are genes that stop cells from dividing –P53-mutated in 50% of cancers –Rb-mutated in 40% of cancers

50. Science, Vol 274. Oct 18,1996. p430

51. Types and causes of mutations Rearrangements –Ionizing radiation- forms free radicals that damage DNA Translocation Duplications Inversions deletions –Spontaneous mutagenesis- slipped mispairing Point mutations –UV light- pyrimidine dimers –Chemical mutagenesis

52. Figure 16.17 Nucleotide excision repair of DNA damage Xeroderma pigmentosum

53. Chemical mutagenesis

54. Ames test Aflatoxin-from the fungus aspergillus that grows on rotting peanuts

55. Viruses cause cancer RNA viruses (retroviruses). Cause cancer by adding oncogenes to cells. –Pick up RNA copies of proto-oncogenes and transfer them to other cells by infection DNA viruses. Cause cancer by blocking tumor-suppressor proteins.

58. Figure 19.13 Genetic changes that can turn proto-ocogenes into oncogenes

59. Viruses cause cancer RNA viruses (retroviruses). Cause cancer by adding oncogenes to cells. DNA viruses. Cause cancer by blocking tumor-suppressor proteins. –Viruses produce proteins that bind to p53 and RB

60. DNA viruses produce proteins that block tumor- suppressor action. Normal Virus infected (SV40/papillomavirus)

62. Not all cancers are alike!