Cancer 1 Flashcards
What did Int1 turn out to be?
Wingless- Wnt
What does Wnt cause in the nucleus?
Beta-catenin accumulates in the nucleus and activates its target genes
Examples of genes activated through Wnt signalling, and what are they involved in
c-Myc
Cyclin D1
They are cell cycle regulators
What are the mutation categories of Wnt signalling
Activating
Loss of repressors
Examples of Wnt signalling repressors
Axin
APC
Wnt5A
What is detected in early colon cancers?
Increased levels of nucelar beta catenin
Which type of cells are Wnt-responsive?
Tissue specific stem cells
What can you do using inbred and genetically modified mice?
- Identify oncogenes/ tumour repressor genes
- Identify signalling pathways that lead to specific tumor types
- Understand the basic biology at a cellular level
What do we want to find out using stem cells in vivo?
- Signalling pathways that are associated with tumour aggression
- Genes that accelerate/slow down cancer
- We want to see multiple systems and the effect cancer has on them
What is involved in the progression of an adenoma to cancer?
The inflammatory pathway
What is an adenoma?
group of cells sitting in a clump- intact
Which factor stimulates an inflammatory role?
Rac1
How do inflammatory signals help cancer metastasise?
Macrophages invade and secrete cytokines- which encourages angiogenesis
They also help break down the ECM
What does Wnt bind to?
Frizzled receptor and low-density lipoprotein related protein (LRP) co receptor
What is the destruction complex which degrades beta catenin? How does it do this
APC CK1 GSK3 AXIN Targets beta catenin for degradation through phosphorylation
What does Wnt do when it gets to the nucleus?
Replaces groucho on the t cell factor transcription factor- creates an active transcriptional complex
How does increased Rac1 lead to hyperproliferation?
Through ROS
(reactive oxygen species)
and
NF-kB
