Cancer 4- apoptosis Flashcards
What are the two main pathways for inducing apoptosis in a cell?
There is the death receptor pathway and in the internal mitochondrial pathway with cytochrome c.
How do tumour cells interfere with apoptotic pathways to induce cancer?
- Tumour cells can disable the death receptor, so that they are resistant to the instruction of cytotoxic t-cells.
- Mutation or downregulation of apoptotic genes through the genome or epigenome can lead to inhibited apoptosis.
How can the p53 tumour suppressor gene induce apoptosis?
The p53 apoptotic gene can induce apoptosis if it detects significant damage to the cell’s genome that cannot be repaired. p53 does this by activating the Bcl internal apoptotic pathway.
How does cancer drug resistance develop with regards to apoptosis?
A lot of cancer drugs work by trying to induce apoptosis of tumour cells. But in most cancers, the tumour cells have already had their apoptotic pathways inhibited. So, the tumours are resistant to these drugs.
How can epigenetic changes induce cancer?
Epigenetics affect the way the DNA genome is expressed. Epigenetic changes include DNA methylation and changes to histones. DNA methylation leads to inhibition of the expression of that gene. Thus DNA methylation of the tumour suppressor gene results in its inhibition, allowing cancer progression.
What are epigenetic writers?
These are epigenetic enzymes which lay down the necessary marks on the particular histone proteins.
what are epigenetic erasers?
These are epigenetic enzymes which can remove the marks placed on the histone markers, if they are incorrect.
what are the epigenetic readers?
These are the epigenetic enzymes which proofread the marks that have been laid down on the histones by the writers. If they are incorrect, then they authorise the erasers to come by.
How can changes to these epigenetic enzymes induce cancer?
These epigenetic enzymes can be mutated and as such result in incorrect epigenetic expression of the genome.
What are the HDAC enzymes and how can they induce cancer?
The HDAC are a family of epigenetic erasers that deacetylate histones. Research has shown that HDAC’s are overexpressed in tumourigenesis, causing oncogene activation. Thus HDAC inhibitors are used as anti-cancer genes because they reverse acetylation of histones.
Bcl-2 pathway antagonists must be used in conjuction with HDAC inhibitors as anti-cancer treament. Why is this?
This is because in cancer, the Bcl apoptotic pathway is inhibited and thus the receptors are desensitised to normal signalling. So, by using antagonists, they can be resensitised .
