Cancer 1 Flashcards
What is cancer characterised by
Unregulated growth facilitated by mutations in cell cycle regulations
What is meant by the term metastatic?
Characteristic of of malignant tumours allowing them to spread
What are adenocarcinomas?
Arise from secretary epithelial cells
What are the names of tumours that arise from epithelial cells?
Carcinoma’s
What does the protective layer of epithelial cells give rise to?
Squamous carcinoma’s
Why do cells in females tumour’s have the same inactive X chromosome?
Because all cells in tumour are derived from single progenitor cells and only one single cell is transformed into cancer cell and cloned to get all of the others
What are the 6 hallmarks of cancer?
- Resisting cell death
- Sustain proliferation signalling
- Evading growth suppressors
- Activating invasion and metastasis
- Enabling replicative immortality
- Inducing angiogenesis
What can enhanced external stimulation of sustained proliferation do to receptors?
Dysregulate them as there is so much growth
What are 3 ways growth signalling autonomy to maintain proliferation can be achieved?
- Mutations in GF receptors - so permanently active therefore kinase is permanently active and signals downstream
- Receptor and level of GF could be normal but have active mutations in key molecules in signalling pathway e.g. PI3-kinase, Ras & Raf
- Mutations in molecules involved in cell cycle
How do cancer cells ‘avoid’ growth inhibiting signals?
Have loss of activity of tumour suppressor genes i.e. p53, PTEN & Retinoblastoma (Rb). And through aberration of TGF-Beta antiproliferative gene (change to its structure)
What are the consequences of PTEN not being activated?
Causes upregulation of Akt-signalling which is very powerful in enhancing cell survival
What does normal PTEN do?
It’s a lipid phosphatase that normally dephosphorylates PIP3 to PIP2
What is the purpose of apoptosis?
To get rid of all the damaged cells essential to maintain DNA fidelity
How do cancer cells avoid apoptosis?
Mutations in molecules affecting intrinsic pathway - loss of p53, upregulation of anti-apoptotic members of BCL-2 family and down-regulation of pro-apoptotic BCL-2 family members.
And mutations in the extrinsic pathway
Where/ when does angiogenesis normally occur?
Embryonic growth, adolescence, female reproductive organs and wound healing
How does angiogenesis occur in tumour growth?
Areas of tumours become hypoxic so require vascularisation and develops its own blood supply.
Tumour will tip balance in favour of molecules that produce angiogenesis
What is the rate limiting step in tumour growth?
Angiogenesis
What is the key molecule implicated in angiogenesis?
VEGF - essential for tumour angiogenesis (vascular endothelial growth factors)
What is different about the blood vessels produced in tumours compared to healthy blood vessels?
Abnormal, leak and don’t have a hierarchy - as in no difference between capillary/ artery etc.
How is VEGF expression upregulated?
By hypoxia and over-activation of other growth factor signalling pathways
What happens in the tumour when areas of it become hypoxic? (5 marks)
- It induces signalling to tumour to make VEGF.
- VEGF binds to its receptor = dimerization.
- Activates a kinase which adds phosphate to the opposite receptor this is known as autophosphorylation.
- After autophosphorylation, proteins containing SH2 domain bind to the phosphorylated receptor and trigger activation of Ras & Raf-MEK-MAPK cascade
- PI3K is also activated and AKT signalling takes place
How is Akt signalling used to promote angiogenesis?
Leads to the inhibition of apoptosis and stimulates endothelial NO synthase and stimulates vascular permeability via NO production
What helps the dilation of blood vessels in angiogenesis?
Nitric oxide - blood vessels need to dilate in order for new ones to spring from it
What is a telomere?
Repetitive DNA sample found on the end of chromosomes and act a a molecular counter
