cancer

What happens to a cell with mutated genes?

• Continue to divide more rapidly

• Fail to stop uncontrolled cell division

• Make mistakes when repairing DNA errors → Accumulation of mutations as they divide

What are proto-oncogenes?

Normal cellular genes which code for proteins involved in the regulation of normal cell division

What happens to proto-oncogenes when they mutate?

• Proto-oncogenes are converted to oncogenes through gain-in-function mutation

• Increase in amount or activity of a proto-oncogene’s protein

• Production of hyperactive, degradation-resistant growth factors/proteins

What mutation mechanisms can lead to the formation of oncogene?

• Gene mutations

• Gene amplification

• Movement of DNA

How does gene mutation result in the formation of an oncogene?

• Point mutation within proto-oncogene → Change in amino acid sequence of proton-oncogene protein → Hyperactive / more resistant to degradation

• Point mutation in base sequences of regulatory elements → Silencer disrupted, cannot interfere with binding of activator to enhancer → Increased transcription → Excess production of growth-stimulating protein

How does gene amplification result in the formation of an oncogene?

• Flaw in normal DNA replication process → Many copies of a region of a chromosome are produced instead of just one → Many copies of that gene

• Proto-oncogene in the amplified region → Number of protons-oncogenes amplified → Excessive production of proto-oncogene protein → Excessive cell division

How does movement of DNA result in the formation of an oncogene?

Chromsomal translocation

• Unusual exchange between chromosomes → Chromosomes break and join at another location, crossing over between non-homologous chromosomes

• Proto-oncogene under the control of an enhancer → Increased transcription → Production of more gene products

How can retroviruses cause cancer?

• Retroviral genome inserts into and inactivates silencer of proto-oncogene

• Retrovirus with own enhancer inserts into host genome → Upregulates transcription of proto-oncogene

• Virus carrying a homologue of the proto-oncogene, which codes for a stronger inducer of cell proliferation

  • Insertion of viral genome → Overall gene product from photo-oncogene is increased

What is the ras gene?

Proto-oncogene involved in signal transduction pathways

How does the Ras gene work?

1. Binding of growth factor to receptor

2. Series of reactions inside the cell → Binding of GTP to an inactive Ras protein → Activates Ras protein

3. Ras protein transduces signals from the growth factor to signaling processes → Cell division

When does the ras gene activate and inactivate?

• Activation ← Need for the cell to divide / when growth factor binds again

• Inactivate ← With own enzymatic activity

What happens to a mutated ras gene?

• Constitutively active Ras protein

• Increased cell division even when the growth factor does not bind to receptor

What are tumour suppressor genes?

• Normal cellular genes that code for products which inhibit cell division, repair damaged DNA and promote apoptosis

• Help prevent uncontrolled cell division

• Products activate cell cycle arrest

What kind of mutation is a mutated tumor suppressor gene?

Loss-of-function mutation

What is the p53 gene?

• Most commonly mutated gene in cancers

• Tumor suppressor gene

• Codes for a specific transcription factor (p53 protein activator) that binds to DNA and activate genes that control the cell cycle

What does the p53 gene do when there is damaged DNA?

• Cell cycle arrest

  • Enough time for cell to repair damaged DNA and prevent production of mutant daughter cells

• DNA repair

  • Preserves genomic integrity and prevents mutations that may lead to formation of oncogenes or inactivate other tumour suppressor genes

hWhat does the p53 gene do when the cell is beyond repair?

Initiate apoptosis → Cell shrinks, DNA and cellular structures get degraded

What happens when a p53 gene is mutated?

• Cell proliferation is not restricted → Cell cycle continues without repairing DNA / undergoing apoptosis

• Accumulation of mutations → Organisms have higher risk of developing cancer cells

What kind of mutation and mutated gene is the oncogene?

• Gain-in-function mutation

• Dominant mutation

What kind of mutation and mutated gene is the tumor-suppressor gene?

• Loss-of-function mutation

• Recessive mutation

What happens when the genes coding for telomerase get mutated?

• Upregulation / activation of genes coding for telomerase → Telomeres become lengthened

• Cell can thus divide indefinitely as chromosomes are prevented from shortening with each DNA replication cycle

What kinds of tumors are there?

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• Benign → Non-cancerous, localized and does not spread to other regions

• Malignant → Benign tumors can transform into cancerous tumours

• Loss of contact inhibition may cause their growth

What are the characteristics of malignant tumors?

• Invasiveness (erodes normal surrounding tissue)

• Ability to undergo metastasis (spread to other parts of the body)

What are some physiological changes that encourage the growth of cancer?

• Loss of contact inhibition → Enabled cells to grow into a tumour

• Angiogenesis (growth of blood vessels within the tumor)

  • Blood vessels formed can transport O₂ and nutrients for growth and remove metabolic waste products and CO₂

Where do the mutations that result in cancer occur?

Accumulation of mutations in a single cell (takes years to accumulate, hence risk increases with age)

What are som causative factors for cancer?

• Hereditary causes

• Chemical carcinogens e.g. smoking, asbestos

• Ionising radiation e.g. UV light

• Loss of immunity e.g. HIV, HPV infection