Sustaining Proliferative Signals Flashcards
What is regulated in homeostasis in normal tissue?
Size of organs kept constant
The number of cells kept similar (proliferation/apoptosis)
Tissue hierarchy
Tissue function
What differences might you notice between microscope images of normal and cancerous [kidney] tissue?
Normal: cortex in the center surrounded by medulla (regular tissue)
Cancerous: tissue hierarchy disturbed, necrosis /growth, aberrant tissue formation
How do cancers lose proliferative signal control?
Cancers can sometime produce their own growth factor signals due to mutations
They therefore express too many growth factors
They also can develop more than the usual number of receptors to detect more signals
Therefore gaining independence from normal regulatory pathways
Outline the simple growth factor (GF) signalling pathway
GF > Receptor targeting kinase (RTK) > Ras > Raf > MEK > ERK
What activates a signalling pathway
Mitogen
What is a Mitogen?
A protein that makes a cell proliferate by activating signalling pathways
What is a PDGF and what does it do?
Platelet Drive Growth Factor
Increases growth and is regulated by tumour cells in glioblastoma
What is the effect of a mutation which elevates receptor levels for signalling pathways?
Increased receptors > increased signals > increased growtth
How are receptor levels on te surface of cells regulated in normal cells?
Receptor targeting kinase systems
A ligand attaches to the receptor which results in te receptor being internalized by the cell so that it cannot receive signals
What happens if a cellular machinery protein involved in the receptor targeting kinase system mutates?
Inappropriate signals could be transmitted
Which may result in the receptor being present back at the surface
What happens if there is a mutation which causes the secondary pathway to be constantly activated?
The RAS pathway is constantly activated
Meaning the downstream events will continue to happen
Therefore the cell will continue to grow/proliferate
What happens if there is a mutation in Raf?
Loses its dependence on RAS
The kinase signal will be activated even in the absence of RAS
Causes excessive proliferation
What factors contribute to tumour growth?
An increase in cell number (increase proliferation ,decrease apoptosis)
An increase in stromal compartment (increase cell invasion)
What is Rb
Retinoblastoma gene
A tumour suppressor gene
What are 2 examples of TSGs?
Rb (retinoblastoma) and TP53
What does TP53 do?
Checks for mutations during cell cycle
If a mutation is present, apoptosis of cell occurs
What activates TP53?
Signs of cell stress / abnormality
Eg: free nucleotides, change in glucose/oxygenation levels
What happens if TP53 is mutated?
There are less checks for mutations
Therefore more mutations are able to go undetected in the cell
What does Rb do?
Regulates cell cycle
What happens if there is a mutation in Rb?
cells proliferate without gatekeepers, increase in mutations, cells grow on top of each other
What is contact inhibition?
When normal cells meet neighboring cells, proteins (integral junctions) on surface bind to each other to stop cells growing abnormally/on top of each other
Why are tumour cells able to grow out of place/n top of each other?
Contact inhibition is lost
The normal signalling pathway for contact inhibition s disturbed
