4.26.2010 2

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4.26.2010 2

  1. 1. 4.26.2010 – Cancer<br /><ul><li>Mutations
  2. 2. Most mutations occur after birth
  3. 3. Environmental mutations
  4. 4. P53 – prevents DNA damage or drives apoposis
  5. 5. No safeguards now to recognize damage and shut cell proliferation down
  6. 6. Benzoapyrene from smoking
  7. 7. Deamination
  8. 8. Replace for thymine –
  9. 9. Andogenous process – liver metabolism
  10. 10. About 50% of cancers are from a mutation in the p53 gene
  11. 11. P53
  12. 12. Tumor suppressor gene (not a protooncogene)
  13. 13. Helps suppress cell proliferation that is abnormal
  14. 14. Retinoblastoma – RB
  15. 15. Holds on to and inhibits transcription factors that drive production of cyclins that move past G1 until phosphorylated by Ras pathway for gene transcription regulation
  16. 16. Restricts mitosis and regulates cell growth in unaltered state
  17. 17. Proto-oncogenes
  18. 18. APC
  19. 19. Ras (ras pathway)
  20. 20. In an overexpressed state, will drive
  21. 21. Src – SH2 domains
  22. 22. Kinase, has SH2 domain, activated in response to RTK
  23. 23. If there is is single allel in a protooncogene that is mutated, it will cause that cell to divide uncontrollably and unregulated
  24. 24. If there is a normal copy on the other allele, a normal cell will divide correctly. However, if both alleles are mutated, that single cell may divide uncontrollably.
  25. 25. Pathways
  26. 26. Ras
  27. 27. GFs activated RTK
  28. 28. Recruit SH2 to activate Ras
  29. 29. Ras activates gene transcription pathways
  30. 30. Myc, when Pi, will lead to enhanced gene expression and enhance cell mitosis
  31. 31. Protonocogene – leads to favored gene expression and poliferation
  32. 32. P16, like p21, inhibits cyclin that binds to cyclin and keeps it from Pi Rb
  33. 33. P16 is a tumor suppressor, restricts cell mitosis
  34. 34. Anti growth factors
  35. 35. TNS – tumor necrosis factor
  36. 36. Growth factor that regulates growth – restricting it
  37. 37. Activates a pathway that turns on inhibitors of cyclins
  38. 38. Binds to RTK
  39. 39. Attacks
  40. 40. Secreted by activated immune cells
  41. 41. P53
  42. 42. Upregulates p21 function
  43. 43. Drives inhibits cyclin dependent kinases and cells stop dividing – senescence – G0
  44. 44. PUMA
  45. 45. Activated by p53 that leads to cells death
  46. 46. Inhibits Bcl2
  47. 47. Makes mitochondrial membrane more unstable
  48. 48. Cytocochrome c is released
  49. 49. Apotosome and caspase 9
  50. 50. Apoptosis
  51. 51. Checkpoints within mitosis
  52. 52. What is regulating G2 and metaphase checkpoints and drive to S phase and see what is required and see if they act as tumor suppressors or proto oncogenes
  53. 53. Examples of Oncogenes
  54. 54. GFs
  55. 55. Overexpression can cause cancers
  56. 56. PDGF – platelet derived growth factor
  57. 57. Sarcomas
  58. 58. Fibrosarcomas
  59. 59. There are two genes (oncogenes) that express amounts of PDGF
  60. 60. V-sis
  61. 61. TRK receptor
  62. 62. Binds to JrK – Nerve Growth factor, neurotrophins, brain derived nuerotrophic factor (BDNF)
  63. 63. Thyroid
  64. 64. Breast
  65. 65. Ras – inability to hydrolzyze GTP to GDp – making it on all the time
  66. 66. Single point mutations
  67. 67. Raf
  68. 68. Src kinase – v-src – sarcomas
  69. 69. Myc – regulated by ras – translocation, aplification, inserional mutagensis – 3 types of cancer
  70. 70. Cyclins – Bcl2 –
  71. 71. Types of Cancer
  72. 72. Carcinomas – Epithelium
  73. 73. Throat lining, skin, intestines
  74. 74. Sarcomas
  75. 75. Muscles or Connective Tissue
  76. 76. Leukias/Lymphomas
  77. 77. Hematopoietic System
  78. 78. Nervous System
  79. 79. Neuromas
  80. 80. Gliomas
  81. 81. Astrocytomas
  82. 82. What types of Mutations are taking place?
  83. 83. Gene amplification
  84. 84. Some muation has caused gene to be respresnted in multiple ways, causing an overexpression of that gene product
  85. 85. Chromsomes rearrangement
  86. 86. Overexpression of proteins that enhance production of that particular gene of interest
  87. 87. Fusio nevent – gene made is on all the time
  88. 88. Her2 receptor
  89. 89. Single mutation in transmembrane region
  90. 90. Thinks bound to GF
  91. 91. Deletion – receptor is always on signaling for cell to divide
  92. 92. TRK receptor
  93. 93. RTK, bound by GFs, autphosphorylation
  94. 94. Mutations: gene rearragnement replaces EXdomain of receptor ith a muscle tropomysoin protein involved in smooth muscle contraction, losing resulatory EXC domain and TRPM is sticking out.
  95. 95. Links with trasmembrane

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