paper 3

• EGFR

  Receptor tyrosine kinase that activates Ras → signal cascade

  
• IGF-1R

  Receptor tyrosine kinase that activates Ras → signal cascade
• TKI

  Small molecule inhibitor that can diffuse through the plasma membrane and then bind to a tyrosine kinase domain of a receptor tyrosine kinase
• TKI

  • Upon binding, it inactivates/inhibits phosphorylation of kinase which blocks the signaling pathway
  • The TKI in the paper is NVP-AEW541
• Ras

  GTP binding protein
• ERK

  MAP kinase that activates effector proteins that trigger cellular response
• Akt

  Focuses on cell survival, inhibits apoptosis
• ESCC cells

  Cancer cells used to determine the effectiveness of the TKI in patients with throat cancer
• Figure 1

  • Uses western blot
  • Three different types of antibodies: P-IGF1R, IGF1R, Actin
  • Experimental control used to ensure data reliability
  • Positive control: HeLa (high expression of IGF1R)
  • Negative control: HFF-1 (low expression of IGF-1R)
  • All ESCC cells have high levels of IGF1R
  • TE-8 and T.Tn cells have low levels of phosphorylated IGF1R
• Figure 3

  • TE-1 and TE-4 indicate cell lysates analyzed were from those cell lines
  • Numbers (0, 0.1, 1, 10) represent concentration of TKI cells were exposed to
  • -/+ signs indicate whether IGF-1 was added to the cells after exposure to the TKI
  • Antibodies used: P-IGF1R, PAkt, PERK1/2
  • The TKI can inhibit the activation of IGF1R and AKT but ERK1/2 (MAPK) is still activated, meaning cancer cells still have a pathway to promote cell proliferation