Genomes-L5-Barriers to Transformed Cells and their Characteristics

how do healthy cells go to fully transformed cells?

acquisition of RIVAL mutations- 10k mutations

• mutation I genes that affect cell division and cell death- cancer

how does cellular society work?

• a division of work- if work isn’t produced- cell death by apoptosis or immune system

• if cell show abnormal behaviour like moving from one tissue to another

• if cells show different peptides- could be an infection or cancer- killed by SEROTOXIN cells

what is it called when a cell moves to another? what cell ARE allowed to move?

metastatic behaviour- when cells moves without permission

• only immune cells

what cells recognise those with abnormal peptide presentation?

serotonin T cells

where do mutations arise from?

1. carcinogens

2. infectious agents that act as carcinogens

3. replication- bp errors- could be advantageous- evolution

what are the major barriers to transformed cells?

1. need growth factors to enable them to divide

2. tumour suppressor genes act as a brake on proliferation

3. cells need oxygen and nutrients- tumours need new blood vessels

4. The immune system acts as a barrier to the development of cancer
   

growth factor- major barrier- what is it and what happens when mutated? give an example

need growth factors- to enable them. provided by paracrine cells

oncogenic mutations have an over expression of growth factor receptor or the growth factor is always ON.

Ras mutation keeps it in an active-GTP bound state

what do tumour suppressor genes act on and what happens when they’re mutated?

an example

• when normal- they stop cell proliferation. they stop cell divide when DNA damage and allow for DNA repair or trigger cell death

when mutated- tumours overcome this machinery. mutation in P53 accumulates DNA damage

p53 is a key tumour suppressor- help in the DNA damage pathway

• ATM proteins- check proteins and activate checkpoint kinase 1 and 2 which ACTIVATE P53

what does P53 do and what does it do when mutated?

p53 is a key tumour suppressor- help in the DNA damage pathway

• ATM proteins- check proteins and activate checkpoint kinase 1 and 2 which ACTIVATE P53

• P53 makes a decision to repair DNA if moderately damage or kill it

example of a chemotherapy type and what does it activate?

Taxol- cause DNA damage and activate P53 to kill the cell BUT tumours have 50% have P53 mutations

cells need oxygen and nutrients- how is this a barrier and how is it overcome?

• in the body- you have enough oxygen and nutrients for the existing cells

• tumours undergo angiogenesis and build new blood vessels by turning on VEGF- vascular endothelial growth factor

how does the immune system act as a barrier?

• immune cells patrol the body- searching for cells with abnormal behaviour

• in development- body undergoes TMB and shown all normal proteins in the body as peptide samples

• abnormal peptides- are recognised by cytotoxic T cells and NK cells

characteristics of transformed cells?

1. are able to grow in lab cultures for long periods of time- untransformed cells cannot- escape hay flick limit

2. reduced need for growth factors

3. anchorage independence

4. altered morphology

5. loss of contact inhibition

what is the hay flick limit? and why does this happen?

untransformed cells have a set number of divisions- usually around 35-40

• telomeres are repetitive DNA sequences at the end of chromosomes- protect coding DNA

• with every division- telomere shortens- who too short the chromosomes fuse together and cells cant divide

how do tumours overcome the hayflick limit?

Tumours overcome the Hayflick limit by activating telomerase- repairs and extends telomeres.

reduced need for growth factors- where is this seen and how does this happen in transformed vs untransformed cells?

a characteristic of a transformed cell

• mutations that allow them to 1) make their own growth factors by autocrine or 1) overexposes growth factor receptors

• normal: GF binds to receptor- receptor dimerises- activates Ras and Raf

• Ras acts downstream- stimulates cell growth

• in cancer- Ras is mutated- binds to GTP easily and stays active without GF stimulation

• b-raf in skin cancer- permenanllty bound to ligand

altered morphology in cancer cells- how so?

in normal cells- very uniform

in transformed- grow very disorganised and alter the skeleton

anchorage independence and loss of contact inhibition- in normal vs transformed cells

• in normal- need to be attached to extracellular matrix- stop growing when they touch other cells(contact inhibition)

• transformed cells- can grow without attachment to the extracellular matrix and lose contact inhibition- can migrate

how are cells tested to see if they’re transformed?

these cells are tested to see if they can form tumours if they’re introduced into an animal

• used in an immunocompromised mouse that lacks T cells due to a mutation in the thymus development- blunts B cell development too