Sustaining Proliferative Signals

Question 1

What is regulated in homeostasis in normal tissue?

Answer 1

Size of organs kept constant
The number of cells kept similar (proliferation/apoptosis)
Tissue hierarchy
Tissue function

Question 2

What differences might you notice between microscope images of normal and cancerous [kidney] tissue?

Answer 2

Normal: cortex in the center surrounded by medulla (regular tissue)
Cancerous: tissue hierarchy disturbed, necrosis /growth, aberrant tissue formation

Question 3

How do cancers lose proliferative signal control?

Answer 3

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

Question 4

Outline the simple growth factor (GF) signalling pathway

Answer 4

GF > Receptor targeting kinase (RTK) > Ras > Raf > MEK > ERK

Question 5

What activates a signalling pathway

Answer 5

Mitogen

Question 6

What is a Mitogen?

Answer 6

A protein that makes a cell proliferate by activating signalling pathways

Question 7

What is a PDGF and what does it do?

Answer 7

Platelet Drive Growth Factor

Increases growth and is regulated by tumour cells in glioblastoma

Question 8

What is the effect of a mutation which elevates receptor levels for signalling pathways?

Answer 8

Increased receptors > increased signals > increased growtth

Question 9

How are receptor levels on te surface of cells regulated in normal cells?

Answer 9

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

Question 10

What happens if a cellular machinery protein involved in the receptor targeting kinase system mutates?

Answer 10

Inappropriate signals could be transmitted

Which may result in the receptor being present back at the surface

Question 11

What happens if there is a mutation which causes the secondary pathway to be constantly activated?

Answer 11

The RAS pathway is constantly activated
Meaning the downstream events will continue to happen
Therefore the cell will continue to grow/proliferate

Question 12

What happens if there is a mutation in Raf?

Answer 12

Loses its dependence on RAS
The kinase signal will be activated even in the absence of RAS
Causes excessive proliferation

Question 13

What factors contribute to tumour growth?

Answer 13

An increase in cell number (increase proliferation ,decrease apoptosis)
An increase in stromal compartment (increase cell invasion)

Question 14

What is Rb

Answer 14

Retinoblastoma gene

A tumour suppressor gene

Question 15

What are 2 examples of TSGs?

Answer 15

Rb (retinoblastoma) and TP53

Question 16

What does TP53 do?

Answer 16

Checks for mutations during cell cycle

If a mutation is present, apoptosis of cell occurs

Question 17

What activates TP53?

Answer 17

Signs of cell stress / abnormality

Eg: free nucleotides, change in glucose/oxygenation levels

Question 18

What happens if TP53 is mutated?

Answer 18

There are less checks for mutations

Therefore more mutations are able to go undetected in the cell

Question 19

What does Rb do?

Answer 19

Regulates cell cycle

Question 20

What happens if there is a mutation in Rb?

Answer 20

cells proliferate without gatekeepers, increase in mutations, cells grow on top of each other

Question 21

What is contact inhibition?

Answer 21

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

Question 22

Why are tumour cells able to grow out of place/n top of each other?

Answer 22

Contact inhibition is lost

The normal signalling pathway for contact inhibition s disturbed