Sustaining proliferative signalling

Question 1

Quick summary of sustaining proliferative signalling

Answer 1

Cell can multiply and divide uncontrollably

Question 2

What is a proto-oncogene

Answer 2

Genes that make sure cell is normally growing- Eg: Ras, Raf, EGFR

Question 3

Ras Oncogene- how its formed and consequence

Answer 3

Point mutation at Glycine
Constant signalling without ligand, therefore sustained proliferation

Question 4

How does Trastuzumab work? (breast cancer)

Answer 4

Monoclonal antibody- blocks HER2 activity
However 70% of people dont respond to treatment

Question 5

How does Erlotinib and Gefitinib work? (NSCLC)

Answer 5

Inhibits Tyrosine Kinase part of EGFR and prevents the signalling pathway being activated in NSCLC

Question 6

EGFR signalling summary:

Answer 6

Ligand causes EGFR to form homodimers or heterodimers
Receptors are phosphorylated in the intracellular tyrosine kinase domain
Triggers intracellular secondary messenger signalling pathway (Ras/ Raf / MapK)
PI3K binding
Endocytosis of activated receptors
Activation of genes

Question 7

What is gene amplification

Answer 7

A mutation where too many copies are made of a gene

Question 8

What is gene rearrangement

Answer 8

A mutation where promotor is in the wrong place- therefore a previously weakly expressed gene is over expressed

Question 9

What is a large structural deletion

Answer 9

A mutation where receptor sequences are deleted, causes truncated EGFR

Question 10

Overview of Chronic Myeloid Leukaemia

Answer 10

Philadelphia chromosomal abnormality
Bcr-Abl activated oncogene
Mimics growth factor activation
activates RTKs which activates RAS , causing phosphorylation of Tyr177

Question 11

Imatinib Mesylate- treatment for CML - how does it work?

Answer 11

Binds with Tyrosine Kinase
Inhibits ATP, Phosphorylation and activation of GFR.