Gene Expression & Cancer (AQA A-Level Biology): Revision Notes
Gene Expression & Cancer
Cancer represents a collection of diseases arising from damage to genes controlling mitosis and the cell cycle. The term originates from Hippocrates 2400 years ago, who observed similarities between swollen veins radiating from breast growths and crab legs.
When genetic damage occurs, cells lose their normal regulatory mechanisms. This leads to uncontrolled mitosis and abnormal cell growth. A tumour forms when a group of abnormal cells develops and continuously expands in size.
Types of tumour
Not every tumour poses the same threat. Tumours fall into two main categories: benign tumours (non-cancerous) and malignant tumours (cancerous). Understanding their differences helps explain treatment approaches and prognosis.
The distinction between benign and malignant tumours is crucial for determining appropriate treatment strategies and predicting patient outcomes.
Comparison of benign and malignant tumours
| Feature | Benign tumours | Malignant tumours |
|---|---|---|
| Growth rate | Grow very slowly | Grow rapidly |
| Size potential | Can grow to large size | Can also grow to large size |
| Cell nucleus | Relatively normal appearance | Often larger and darker due to abundant DNA |
| Cell differentiation | Well differentiated (specialised) | Become de-differentiated (unspecialised) |
| Cell adhesion | Produce adhesion molecules, stick together, remain localised (primary tumours) | Do not produce adhesion molecules, spread via metastasis to form secondary tumours |
| Structure | Surrounded by dense tissue capsule, compact structure | Not capsulated, grow finger-like projections into surrounding tissue |
| Health impact | Less likely to be life-threatening, but can disrupt vital organ function | More likely to be life-threatening as abnormal tissue replaces normal tissue |
| Effects | Localised effects on the body | Systemic effects including weight loss and fatigue |
| Treatment | Usually removed by surgery alone | Requires combination of radiotherapy, chemotherapy and surgery |
| Recurrence | Rarely reoccur after treatment | More frequently reoccur after treatment |
Cancer and the genetic control of cell division
DNA analysis of tumours reveals that cancer cells typically originate from a single mutant cell. An initial mutation triggers uncontrolled mitosis, while subsequent mutations in descendant cells create further abnormalities in growth and appearance.
Two main gene types regulate cell division and play crucial roles in cancer development: tumour suppressor genes and oncogenes.
Oncogenes
Oncogenes develop from mutations in proto-oncogenes. Proto-oncogenes normally stimulate cell division when growth factors bind to protein receptors on cell surface membranes. This binding activates genes promoting DNA replication and cell division.
How Proto-oncogenes Transform into Oncogenes:
A proto-oncogene transforms into an oncogene through permanent activation via two mechanisms:
Mechanism 1: The receptor protein becomes permanently activated, maintaining cell division even without growth factors present
Mechanism 2: The oncogene produces excessive amounts of growth factor, continuously stimulating cell division
Result: Rapid, uncontrolled cell division leading to tumour formation
Most cancer-causing mutations involving oncogenes are acquired during a person's lifetime rather than inherited.
Tumour suppressor genes
Tumour suppressor genes function as cellular brakes, slowing cell division, repairing DNA errors, and triggering apoptosis (programmed cell death) when cells become damaged. Normal tumour suppressor genes maintain controlled cell division rates, preventing tumour formation.
When tumour suppressor genes become mutated and inactivated, they lose their inhibitory function. This allows uncontrolled cell division to proceed. The mutated cells often differ structurally and functionally from normal cells. Most survive and can clone themselves to form tumours.
Important tumour suppressor genes include TP53, BRCA1 and BRCA2. The TP53 gene codes for the p53 protein involved in apoptosis. More than half of human cancers show abnormalities in TP53, affecting DNA repair and programmed cell death processes.
Key Distinction: Oncogenes cause cancer through activation of proto-oncogenes, while tumour suppressor genes cause cancer when they become inactivated.
Abnormal methylation of tumour suppressor genes
DNA methylation plays a significant role in gene expression regulation. Abnormal methylation patterns commonly occur during tumour development, with hypermethylation (increased methylation) being the most frequent abnormality.
Hypermethylation effects
Step-by-step Process: How Hypermethylation Contributes to Cancer
Step 1: Hypermethylation occurs specifically in promoter regions of tumour suppressor genes
Step 2: This leads to tumour suppressor gene inactivation
Step 3: Transcription of promoter regions becomes inhibited
Step 4: The tumour suppressor gene becomes silenced (switched off)
Step 5: Since tumour suppressor genes normally slow cell division rates, their inactivation results in increased cell division and tumour formation
BRCA1 represents a tumour suppressor gene where abnormal methylation contributes to breast cancer development.
Hypomethylation effects
Hypomethylation (reduced methylation) can also contribute to cancer when it occurs in oncogenes, leading to their activation and subsequent tumour formation.
Oestrogen concentrations and breast cancer
Oestrogens regulate the menstrual cycle in women. Following menopause, when ovarian oestrogen production diminishes, a woman's breast cancer risk paradoxically increases. This occurs because fat cells in breast tissue continue producing oestrogens locally after menopause.
Mechanism of oestrogen-induced cancer
Oestrogen can trigger tumour development through its effect on gene expression. When oestrogen binds to genes controlling cell division and growth, it activates these genes. Continued activation promotes ongoing division that can produce tumours.
Mechanism: How Oestrogen Leads to Breast Cancer
Initial Process: Oestrogen causes proto-oncogenes in breast tissue cells to develop into oncogenes, leading to breast cancer formation
Positive Feedback Loop:
- Once a tumour develops, it further increases local oestrogen concentrations
- This accelerates tumour growth
- White blood cells attracted to the tumour site increase oestrogen production
- This creates a positive feedback loop promoting even greater tumour development
Key Points to Remember:
- Cancer develops when genes controlling cell division become damaged, leading to uncontrolled cell growth
- Benign tumours remain localised and grow slowly, while malignant tumours spread rapidly through metastasis
- Oncogenes cause cancer when activated, tumour suppressor genes cause cancer when inactivated
- Hypermethylation of tumour suppressor genes silences them, contributing to cancer development
- Oestrogen can activate proto-oncogenes in breast tissue, leading to breast cancer formation