Lecture 8 - Areas of current development

Question 1

How do epigenetics play a role in cancer development?

Answer 1

• Methylation or acetylation silencing or expressing tumour suppressor genes or oncogenes
• dysregulation of the epigenetics can cause changes in the expression of TSG or OG

Question 2

What does a methylated gene correlate with?

Answer 2

Represses gene transcription

Question 3

What does an acetylated gene correlate with?

Answer 3

Promotes gene transcription

Question 4

P53 promotes a lncRNA leading to gene repression of what sorts of genes?

Answer 4

Cell proliferation and cell survival genes

Question 5

miRNAs lead to…

Answer 5

transcriptional repression or mRNA degradation

Question 6

If an enzyme which is responsible for acetylation is mutated in cancer, what does this tell you about the gene it normally regulates?

Answer 6

Likely to be a tumour suppressor gene

Question 7

Which genes may be targeted by methylation in CANCERS (therefore not normal)?

Answer 7

Hypermethylation of TSG in cancers

Question 8

If you methylated the DNMTs what would be the effect?

Answer 8

• If you methylated a DNMT you don’t express the enzymes, so genes which should be getting methylated aren’t getting methylated so if these are oncogenes this could cause cancer

Question 9

What is the more common epigenetic modification which occurs to cause cancer?

Answer 9

Suppression of tumour suppressor genes

Question 10

How do DNA methylation inhibitors work but what is their issue?

Answer 10

Can cause DNA instability and apoptosis of tumour cells but methylation returns if drug is stopped.

Question 11

What are tumour cells actually primed for, and how could we utilise this?

Answer 11

Actually primed for apoptosis, if we could inhibit Inhibitors of Apoptosis (IAPs) we could remove them and tumour cells would self implode with the activated caspases

Question 12

What are there high levels of in tumour cells which makes us think they are primed for apoptosis?

Answer 12

• activated caspases
• most caspases in WT cells are inactive as you don’t want to kill WT
• however in tumour cells most have been cleaved and are pre activated but inhibited by high levels of inhibitors of apoptotic proteins
• tumour cells overexpress IAPs

Question 13

What can loss of caspase expression be due to?

Answer 13

• Hypermethylation of the promoter
• Deletions and mis-sense mutations