Cancer Flashcards
Define cancer.
Cancer occurs when there is dysregulation in the cell cycle checkpoints which leads to uncontrolled cell division. This happens when the rate of cell division exceeds the rate of cell death.
What is metastasis?
Metastasis is when cancerous cells break free from its primary site/tumour and enter the blood or lymphatic system to invade other tissues and form a secondary tumour.
Explain how the dysregulation of cell cycle checkpoints may lead to accumulation of mutation and cancer development.
When there is dysregulation in checkpoints , DNA damage cannot be repaired. Gene mutation will be passed onto daughter cells. Daughter cells will have gain of function mutation to proto-oncogenes and loss of function to tumour suppresor gene. This will cause uncontrolled cell division where rate of cell growth is higher than rate of cell death , forming a tumour.
Mechanisms of mutation that converts proto-oncogene into oncogene.
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-Chromosomal translocation ; proto-oncogene may move from its original site to a different location in the chromosome. This may cause the proto-oncogene to be downstream a more active promoter/another control element/highly active enhancer. Proto-oncogene is overexpressed , forming excessive amount of protein.
-Gene amplification ; Processes like error in DNA replication may generate multiple copies of proto-oncogene , causing it to be over-expressed and lead to excessive formation of protein.
-Gene mutation within control element ; mutation occurs in the promoter or enhancer that controls the proto-oncogene , overexpression of proto-oncogene and excessive formation of protein.
-Gene mutation within gene ; Mutation in exons of the proto-oncogene. This would cause a change in the amino acid sequence of the protein , altering the tertiary structure/conformation of protein. Protein might be constitutive or resistant to degradation.
-Retroviral integration ; Integrates viral DNA into proto-oncogene and converts it into oncogene.
What is ras protein?
It is a G protein involved in signal transduction pathway to indirectly stimulate cell division. Ras protein is only active in the presence of a single/growth factor.
Ras undergoes what mechanism of mutation?
Ras proto-oncogene will convert into ras oncogene when mutated. Ras protein is constitutive and is still stimulates the pathway even without the presence of a signal/growth factor. This leads to uncontrolled cell growth and cell division , causing cancer.
What is the example of proto-oncogene leading to cancer formation?
C-myc gene coding for c-myc protein. C-myc protein is a transcription factor that simulates expression of other gene to stimulate cell division. In cancer , c-myc proto-oncogene is moved from chromosome 8 to chromosome 14. C-myc proto-oncogene is now downstream a highly active enhancer , converting c-myc proto-oncogene into c-myc oncogene. This causes excessive production of c-myc protein causing cancer.
Function of tumour-suppresor genes
-Genes that codes for proteins that inhibit cell growth and division in normal cells.
-Genes that codes for proteins that activate apoptosis
-Genes that for activating DNA repairing genes
-Genes that code for protein to combat angiogenesis
How does TSG undergoes mutation?
It becomes inactive and codes for non-functional protein. TSG will undergo loss of function mutation where only both alleles have to be mutated to produce non-functional tumour suppresor proteins as if only one allele is mutated , the other allele cam still code for sufficient functional protein.
Features of mutated TSG
Loss of DNA repair
Loss of apoptosis during DNA damage
Loss of cell cycle control and inappropriate cell cycle progression.
p53 function
It is a transcription factor that binds to promoter/enhancer to stimulation the expression of many different genes when there is DNA damage.
-genes involved in dna repair
-genes involved in apoptosis when dna damage is beyond repair
-genes involved in blocking angiogenesis.
p53 eg in lecture notes
p53 goes through loss of function mutation resulting in the absence of a transcription factor. Genes that are usually expressed when there is DNA damage are not expressed. Cell cycle does not stop for DNA damage , there will be no repairing of DNA damage due to the absence of DNA repairing proteins. Damages cells does not undergo apoptosis and continues to divide , giving rise to mutated daughter cells. This allows for accumulations of further mutations. Angiogenesis occurs , allowing spread of tumour cells.
This results in uncontrolled cell division and cell growth , causing cancer.
Explain the significance of haploid gametes.
It restores the diploid number when the nuclei of gametes fuse during fertilization. Allows for combination of genetic material from 2 parents , leading to genetic variation.
Role of centromeres.
Non- coding DNA sequence that holds sister-chromatids together. Allows for the alignment of chromosomes on metaphase plate.
