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RELEVANT LEARNING OUTCOME:
(d) Explain how the loss of function mutation of tumour suppressor genes, including p53, and gain in function mutation of proto-oncogenes, including ras, results in uncontrolled cell division.
How cancer forms
How cancer forms
👁️🗨️Watch the video to learn about how a single cell in a tissue undergoes transformation, the process that converts a normal cell to a cancer cell.
Transformation occurs when there is an accumulation of mutations in several genes, including those regulate the cell cycle like proto-oncogene and tumour suppressor gene.
🖊️Check Your Understanding: Learning Goals Checkpoint
🖊️Check Your Understanding: Learning Goals Checkpoint
1. Why does dysregulation of cell cycle checkpoints lead to cancer?
1. Why does dysregulation of cell cycle checkpoints lead to cancer?
No checking of DNA damage
Accumulation of mutations in genes that regulate the cell cycle like proto-oncogene and tumour suppressor gene
Uncontrolled cell division leads to cancer formation
Genes involved in cancer development
Genes involved in cancer development
In cancerous cells, mutations have occurred that alter the production of some proteins, leading to dysregulated cell cycle checkpoints and abnormal cell behaviour.
The loss of function mutation of tumour suppressor genes e.g. p53, and gain in function mutation of proto-oncogenes e.g. ras, results in uncontrolled cell division.
Oncogene vs Tumor Suppressor Gene
Oncogene vs Tumor Suppressor Gene
👁️🗨️Watch the video and answer the questions below:
What are proto-oncogenes and tumor suppressor genes?
What are gain-of-function and loss-of-function mutations?
How does oncogene (mutated form of proto-oncogene) cause uncontrolled cell division?
What is 'two hits' mechanism?
How does loss-of-function mutation of tumor suppressor gene cause uncontrolled cell division?
How proto oncogene becomes an oncogene
How proto oncogene becomes an oncogene
👁️🗨️Watch the video to learn about 2 mechanisms that convert a proto oncogene to oncogene
chromosomal translocation (e.g. c-myc oncogene)
gene amplification
🖊️Check Your Understanding: Conceptual Check 4
🖊️Check Your Understanding: Conceptual Check 4
What is the difference between gain-of-function mutation and loss-of-function mutation in terms of the nature of mutation?
Gain-of-function mutation
Dominant
Only one mutated allele is needed
Loss-of-function mutation
Recessive
Requires both alleles of the gene to be mutated/deleted
2. What is the difference between gain-of-function mutation and loss-of-function mutation in terms of the effect of mutation?
Gain-of-function mutation
Production of overactive proteins, or excessive production of proteins
The mutated proto-oncogene is known as oncogene.
Loss-of-function mutation
Tumour supressor genes are inactivated and no longer code for functional proteins.
3. What is the difference between gain-of-function mutation and loss-of-function mutation in terms of how it leads to cancer?
Gain-of-function mutation
Over-stimulation of cell cycle / excessive growth signal
Loss-of-function mutation
Normal function of cell cycle arrest is lost, leading to cancer because of
o Loss of ability for DNA repair.
o Loss of apoptosis when DNA is damaged.
o Loss of cell cycle control and inappropriate cell cycle progression.
4. What are some examples of gain-of-function mutation and loss-of-function mutation?
Gain-of-function mutation
Mutations that convert proto-oncogenes to oncogenes, such as ras gene and c-myc gene.
Loss-of-function mutation
Mutations in p53 gene
Telomeres and telomerase
Telomeres and telomerase
👁️🗨️Watch the video to learn about
What are telomeres?
Actions of telomerase that will delay the degradation of telomere
Cells expressing telomerase can undergo unlimited cell division and possibly leading to cancer.
🕹️ SLS Activity
🕹️ SLS Activity
Complete the SLS Assignment to reinforce your understanding of Uncontrolled Cell Division
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