Biochemistry 3 Flashcards
What does cancer depend upon the accumulation of?
changes in somatic cells
What can give rise to cancerous cell behaviour?
mutations and epigenetic changes
What does ‘cancer-critical’ refer to?
all genes whose alteration contributes to, causing or evolution of, cancer by driving tumourigenesis (tumour development)
How do tumours develop?
- cancer cells grow and proliferate, unregulated by normal control mechanisms
- they may become able to invade surrounding tissues and remove organs - metastasis
Where are cancers thought to originate from?
- a single cell that has mutated and then acquired additional abnormalities
- these changes increase the ability of the cancer cells to survive, grow and divide and then to metastasise, grow at other sites
What is selected for in the clones of aberrant cells able to produce tumours, and why?
- genetic and/or epigenetic instability
- the instability accelerates accumulation of genetic and/or epigenetic changes required for tumour progression
In what 2 ways can a genome be disrupted?
- in some cases the karyotype at mitosis appears normal - indicating there must be point mutations in individual genes - therefore failure of repair mechanism
- karyotype severely abnormal with chromosome breaks and rearrangements
What are the 2 main classes of cancer-critical genes?
- proto-oncogenes
- tumour-suppressor genes
What are proto-oncogenes?
- where a gain-of-function mutation can drive a cell towards cancer
- mutant, overactive or over-expressed forms of these genes are called oncogenes
What are tumour-suppressor genes?
- where loss of function mutation(s) can contribute towards cancer
e.g. TP53
How many of the genes in the human genome are cancer critical?
approximately 1% (~300)
What does ‘loss of function’ mean?
generally refers to the tumour suppressor genes, where loss of function leads towards cancer development
What does ‘gain of function’ mean?
generally refers to a situation where gain of function leads towards cancer development
e.g. when proto-oncogenes are mutated, overactive or over-expressed (now called oncogenes)
What 3 key pathway are often found to be damaged in tumours?
- p53 pathway
- Rb pathway
- RTK/Ras/PI3K
What is the importance of the p53 pathway?
genes within the pathway that regulate responses to stress and DNA damage
- protective function over the genome
What is the importance of the Rb pathway?
Rb itself and genes that regulate Rb (retinoblastoma)
- involved in initiation of the cell division cycle
What is the importance of the RTK/Ras/PI3K pathway?
this pathway transmits signal for cell growth and division from the outside of the cell into the cell
What is the protein function of TP53 gene (a tumour suppressor gene)?
transcription factor
What is the protein function of RB1 gene (a tumour suppressor gene)?
transcriptional Co-Repression
What is the protein function of PTEN gene (a tumour suppressor gene)?
Lipid phosphotase (phosphoinositide metabolism)
What is the protein function of BRCA1 gene (a tumour suppressor gene)?
DNA repair, cell cycle control, genomic stability
What is the protein function of ARF gene (a tumour suppressor gene)?
MDM2 Antagonist (p53 stability)
What is the protein function of NF1 gene (a tumour suppressor gene)?
GTPase Activating Protein for Ras
What gene is p53 encoded by?
TP53
