Gene Expression and Cancer - 20.5

Question 1

What is cancer?

Answer 1

A group of diseases caused by damage to the genes that regulate mitosis and the cell cycle. The leads to unrestrained growth of cells, leading to a tumour.

Question 2

What are the two types of tumour and which one is cancerous?

Answer 2

• Malignant - cancerous

- Benign - non-cancerous

Question 3

What are some of the main features of malignant tumours?

Answer 3

• Can grow to a large size.
• Grow rapidly.
• Cell nucleus is often larger and appears darker due to an abundance of DNA.
• Cell become de-differentiated (unspecialised).
• Cells do not produce adhesion molecules - metastasis, forming secondary tumours.
• Tumours are not surrounded by a capsule - grow finger-like projections.
• More likely to be life threatening, as abnormal tumour tissue replaces normal tissue.
• Often have systematic (whole body) effects such as weight loss and fatigue.
• Removal usually involves radiotherapy and/or chemotherapy as well as surgery.
• More frequently reoccur after treatment.

Question 4

What are some of the main features of benign tumours?

Answer 4

• Can grow to a large size.
• Grow very slowly.
• The cell nucleus had a relatively normal appearance.
• Cells are often well-differentiated (specialised).
• Produce adhesion molecules so remain within the tissue.
• Tumours surrounded by capsule so remain as a compact structure.
• Much less likely to be life threatening but can disrupt functioning of vital organ.
• Tend to have localised effects on the body.
• Can usually be removed by surgery alone.
• Rarely reoccur after treatment.

Question 5

What has DNA analysis of tumours shown?

Answer 5

Cancer cells are derived from a single mutant cell. The initial mutation causes uncontrolled mitosis in this cell. Later, a further mutation in one of the descendent cells leads to other changes that cause subsequent changes to be different from normal growth and appearance.

Question 6

What are the two main types of genes that play a role in cancer?

Answer 6

• Oncogenes.

- Tumour Suppressor Genes.

Question 7

What are oncogenes?

Answer 7

Most oncogenes are mutations of proto-oncogenes.

Question 8

What do proto-oncogenes do?

Answer 8

Stimulate a cell to divide when growth factors attach to a protein receptor on its cell surface membrane. This then activates genes that cause DNA to replicate and the cell to divide.

Question 9

What happens if proto-oncogenes mutate?

Answer 9

If a photo-oncogene mutates into an oncogene it can become permanently activated (switched on).

Question 10

What are the two reasons as to why an oncogene can become permanently switched on?

Answer 10

• The receptor protein on the cell-surface membrane can be permanently activated, so that cell division is switched on even in the absence of growth factors.
• The oncogene may code for a growth factor that is then produced in excessive amounts, again stimulating excessive cell division.

Question 11

What happens if an oncogene is permanently switched on?

Answer 11

The result is that cells divide too rapidly and out of control, and a tumour or cancer, develops.

Question 12

How are cancers caused in relation to photo-oncogene?

Answer 12

A few cancers are caused by inherited mutations of proto-oncogenes that cause the oncogene to be activated but most cancer-causing mutations involving oncogenes are acquired, not inherited.

Question 13

What do tumour suppressor genes do?

Answer 13

They slow down cell division, repair mistakes in DNA, snd ‘tell’ cells when to die in a process called apoptosis (programmed cell death).

Question 14

What is the job of a normal tumour suppressor gene and what happens when they mutate?

Answer 14

A normal tumour suppressor gene maintains normal rates of cell division and so prevents the formation of tumours. If a tumour suppressor gene becomes mutated it is inactivated, meaning it stops inhibiting cell division and cells can grow out of control.

Question 15

What happens as a result of the mutated cells due to mutated tumour suppressor genes?

Answer 15

While most of these die, those that survive can make clones of themselves and form tumours.

Question 16

How are cancers caused in terms of tumour suppressor genes?

Answer 16

Some cancers are caused by inherited mutations of tumour suppressor genes but most are acquired.

Question 17

What is an example of a gene mutations resulting in cancer?

Answer 17

More than half of human cancers display abnormalities of the TP53 gene (which codes for the p53 protein). Acquired mutations of the TP53 gene occur in many cancers, including lung and breast cancer.

Question 18

What does the p53 protein do and how does a mutation in the coding gene affect the human body?

Answer 18

The p53 protein is involved in apoptosis (programmed cell death). This process is activated when a cell is unable to repair DNA. If the gene for p53 is not functioning correctly, cells with damaged DNA continue to divide leading to cancer.

Question 19

What is the main difference between oncogenes and tumour suppressor genes?

Answer 19

While oncogenes cause cancer as a result of the activation of photo-oncogenes, tumour suppressor genes cause cancer when they are inactivated.

Question 20

What is the process by which hypermethylation takes place?

Answer 20

• Hypermethylation (increased methylation) occurs in the promoter region of tumour suppressor genes.
• This leads to the tumour suppressor gene being inactivated.
• As a result, transcription of the promoter regions of tumour suppressor genes is inhibited.
• The tumour suppressor gene is therefore silenced.
• As the tumour suppressor gene normally slows the rate of cell division, its inactivation leads to increased cell division and the formation of a tumour.

Question 21

Where is hypermethylation thought to occur?

Answer 21

Abnormal methylation of this type is thought to occur in a tumour suppressor known as BRACA1 and leads to the development of breast cancer.

Question 22

What is another form of abnormal methylation?

Answer 22

Another form of abnormal methylation is hypomethylation (reduced methylation). This has been found to occur in oncogenes where it leads to their activation and hence the formation of tumours.

Question 23

How does oestrogen link to the formation of breast cancer?

Answer 23

It is thought that increased oestrogen levels can increase a woman’s risk of developing breast cancer.

Question 24

How does menopause link to the development of breast cancer?

Answer 24

The fat cells of the breast tend to produce more oestrogen after the menopause. These locally produced oestrogen appear to trigger breast cancer in postmenopausal women. Once a tumour has develops it further increases oestrogen concentration which therefore leads to increased development of the tumour.

Question 25

How does oestrogen link to proto-oncogenes?

Answer 25

Oestrogen causes proto-oncogenes of cells in breast tissue to develop into oncogenes. This leads to the development of a tumour.

Question 26

What is a carcinogen?

Answer 26

A chemical, a form of radiation, or other agent that causes cancer.

Question 27

What are the main factors affecting a persons likelihood of developing cancer?

Answer 27

• Smoking.
• Diet.
• Obesity.
• Physical activity.
• Sunlight.

Question 28

What wavelengths of Ultraviolet light are the most dangerous and where are they found?

Answer 28

Wavelengths between 250 to 270 nm are the most dangerous and are found in bright sunshine, particularly since the ozone has become depleted in the upper atmosphere.

Question 29

How does UV light (non-ionising radiation) cause cancer?

Answer 29

UV-light energy is absorbed by the nitrogenous bases in DNA and result in the formation of thymine dimmers. These couple across the DNA instead of thymine coupling to adenine, causing the DNA to develop abnormal bulges. Most people have an enzyme that repairs the DNA but some people have a gene mutation that causes the repair enzyme to be damaged, and this allows cancer to develop.

Question 30

What type of cancer is associated with UV light and why?

Answer 30

Skin cancer as UV-light cannot penetrate further than the epidermis.

Question 31

How do X-rays and gamma-rays (ionising radiations) cause cancer?

Answer 31

X-rays and gamma-rays act by:

• Directly breaking DNA and RNA into short lengths
• Splitting water into reactive ionised fragments with damaged DNA indirectly.

Question 32

What types of cancer are associated with ionising radiation?

Answer 32

• Lung.
• Breast.
• Bone marrow cancers.

Question 33

How do mutagenic chemicals (polycyclic hydrocarbons, nitrosamines, aromatic amines) cause cancer?

Answer 33

Mustard gas adds a methyl or similar alkyl group to guanine altering its ability to base pair. This causes the release of guanine from DNA so that the position occupied by guanine can then be filled by another base.
Many other chemicals are base analogues which have similar structures to the normal bases and so can become incorporated into the DNA in place of them during replications.

Question 34

Where are polycyclic hydrocarbons found?

Answer 34

Soot and tobacco smoke

Question 35

How can certain viruses lead to the development of cancer?

Answer 35

Some viruses can contain genes that when inserted into the host cells DNA become oncogenes. DNA viruses such as the Epstein-Barr virus contain their own oncogenes, which when inserted into the host’s DNA cause uncontrolled cell division.

Question 36

What type of cancer is associated with viruses?

Answer 36

Cervical cancer (linked to papilloma virus).

Question 37

What uncontrollable factors can cause cancer?

Answer 37

• Age.

- Genetic predisposition.

Question 38

How can genetic predisposition lead to cancer?

Answer 38

The genes involved may be oncogenes, or genes that stop the immune system from recognising and attacking cancer cells therefore allowing the development of tumours,.

Question 39

How can tumours arise?

Answer 39

The tumours arise from problems with the mechanisms responsible for the control of cell division. The problems may be due to:

• Mutations
• Abnormal activation of the genes involved.

Question 40

What is the primary tumour?

Answer 40

If abnormal cells are not recognised by the immune system and suppressed, they will multiply uncontrollably, resulting in the formation of a bundle of identical cells, called the primary tumour.

Question 41

What are the two ways in which a tumour can break away and spread to other parts of the Body?

Answer 41

• The tumour cells become mobile by amoeboid action (then called ‘tadpole cells’) and can migrate into nearby areas.
• The tumour cells can be transported in the bloodstream and the lymphatic system.

Question 42

What is metastasis?

Answer 42

The process of invasion of other body tissues by cells from the primary tumour. this gives rise to secondary tumours or metastases in organs such as the liver, adrenal glands and the brain.

Question 43

What is the difference between tumours formed from tumour cells transported in the blood and those transported in the lymph?

Answer 43

If the tumour cells are transported in the blood, the secondary tumour is likely to be distant from the primary tumour, however if the transport system is the lymph, it is most likely to occur in a lymph node close to the original tumour.

Question 44

What is melanin and what does it do?

Answer 44

A skin pigment that provides some protection by absorbing the radiation.

Question 45

What is Melanoma?

Answer 45

A highly malignant tumour, which often forms secondary tumours in the brain, resulting in death.

Question 46

What are some ways in which cancer can be diagnosed?

Answer 46

• X-rays.
• Ultrasound scanning.
• Computerised tomography (CT).
• Magnetic resonance imaging (MRI).
• Blood sample.
• Monoclonal antibodies.

Question 47

What is the problem with diagnosing using tools such as x-rays?

Answer 47

The success of these techniques relies on the presence of a tumour that is large enough to be detected.

Question 48

How can monoclonal antibodies be used to help diagnose cancer?

Answer 48

The use of monoclonal antibodies allows the recognition of the different antigens on cells. The monoclonal antibodies are tagged with harmless radioactive tracers (radionuclides) which emit gamma-rays. As the tracer collects at clumps of cancer cells it can be visualised by gamma scanning. A 3D image of the tumour and its position can be built up and this enables radiotherapy treatment to be accurately directed.

Question 49

What are the main treatments used to treat cancer?

Answer 49

• Surgery
• Radiotherapy of the affected area using x-rays to kill tumour cells.
• Chemotherapy of the whole body using chemicals which kill dividing cells, including normal and tumour cells.
• Chemotherapy using drugs, which reduce the risk of developing of breast tumours by reducing oestrogen levels,

Question 50

What does the term ‘magic bullets’ refer to in terms of cancer?

Answer 50

Anti-cancer drugs can be attached to the antibody and thus delivered to the desired sire; these are the so called magic bullets.

Question 51

How is research being used to try and find a more natural treatment for cancer?

Answer 51

A natural means of defence against cancer is the immune system, and research is being directed towards finding a way to stimulate immune reactions, for example, by using interferons and interleukins produced by genetically modified bacteria.

Question 52

What is another way that monoclonal antibodies can be used to help treat cancer?

Answer 52

Another technique is to tag monoclonal antibodies with an enzyme that converts the inactive form (prodrug) of an anti-cancer drug into an active form. The prodrug is then administered in high doses, but will only be activated at cancer cells by the presence of the enzyme, thus killing them, while not having any effect on non-cancerous cells. This technique is called ADEPT (Antibody Direct Enzyme Prodrug Therapy).