Lecture 25: Cancer II

Question 1

Tumor Suppressor genes

Answer 1

• Encode proteins that inhibit cell proliferation
• 2 major categories
  
  • Proteins that normally restrict cell growth and proliferation
    
    • intracellular proteins that inhibit progression through G₁ in cell cycle (e.g. Rb, CKI)
    • Receptors or components of a signaling pathway that inhibit cell proliferation
    • Proteins that promote poptosis (caspase)
  • proteins that maintain integrity of the genome
    
    • Checkpoint control proteins (ATM, ATR- detect DNA damage- stop cell cycle)
    • DNA repari enzymes or pathways
• (note if these tumor suppressor genes are lost then cancer can occur)

Question 2

Retinoblastoma

Answer 2

• Inherited eye cancer in children
• Rb is a tumor suppressor
  
  • prevents over-proliferation of cells
  • loss of copies of both Rb genes leads to cell and tumor proliferaiton of retina

Question 3

Oncogenes vs. Tumor Suppressor Genes

Answer 3

• Overactivity mutation/gain of function
  
  • Oncogenes
    
    • involves single mutation event and activation of gene causing proliferation (dominant)
    • gas pedal
• Underactivity/loss of function
  
  • Tumor suppressor genes
    
    • involve genes that inhibit growth
    • mutation even:
      
      • one gene= no effect
      • second mutation causes problesm thus recessive
      • The brakes

Question 4

_____ is a normal gene, usually involved in regulation of cell proliferation that can be converted to a cancer-causing oncogene by a mutation

Answer 4

Proto-oncogene

Question 5

p53

Answer 5

• Huge tumor suppressor gene
• involved in:
  
  • cell cycle arrest
  • DNA repair
  • Apoptosis
  • Block of angiogenesis
• if you lose p53 then you lose several functions:
  
  • Loss of checkpoint control in cell cycle
  • loss of cell cycle arrest in response to DNA damage
  • loss of DNA repair activities
• stimulates transcription of gene enoding CKI (Cdk inhibitory protein) called p21
  
  • p21 binds to G₁/S-Cdk and S-Cdk and so will stop cell cycle
• p53 also activates expression of pro-apoptotic proteins BH123 and BH-3 only

Question 6

Viral proteins of papilloma virus that cuase malgnancy are

Answer 6

E6 and E7 (they bind to 2 tumor suppressor genes: Rb + p53)

Question 7

In a normal cell Rb binds to ___ protein (gene regulatory protein) to inactivate transcription of cyclins and production of G₁/S-Cdk and S-Cdk does not happen

Answer 7

E2F

Question 8

Viral protein ___ binds to Rb and so E2F (gene regulatory protein) can cause overexpression of G₁/S-Cdk and S-Cdk and cells grow and divide and viral protein ____ binds to p53 and inactivates it so CKI is not produced and Cdk’s can act uncontrollably

Answer 8

E7, E6

Question 9

colorectal cancer takes ___ years for tumor progression

Answer 9

10 years

Question 10

What is the precursor to colorectal cancer

Answer 10

Polyp

Question 11

Patients with Familial adenomatous polyposis coli (FAP) have inactivating mutations or delations of one copy

Answer 11

of APC

Question 12

Chemotherapy has an impact on rapidly dividing cells… give examples of some side effects of this

Answer 12

• Follicle cells produce hair
  
  • loss of hair
• Stomach-lining cells
  
  • Nausea
• Blood-producing cells
  
  • Anemia and immune dysfunction

Question 13

Bcr-Abl

Answer 13

• Abl is a tyrosine kinase for cell signaling
• N-terminus Bcr makes it hyperactive
• Bcr-Abl makes highly active tyrosine kinases
  
  • causes cell proliferation- cancer chronic myelogenous leukemia (CML)
• Treated with
  
  • Gleevec
    
    • inhibits tyrosine kinase activity
    • takes place of ATP on Bcr-Abl and