Cancer

Proto-oncogenes

Encode for proteins that stimulate normal cell growth and cell division

Proto-oncogenes → oncogenes

Gain in function mutation

• Results in increase in expression of normal gene product

• Is a dominant mutation as only one allele of a gene needs to be mutated

Ras proto-oncogene

• G protein that relays a signal from growth factor that results in a cellular response that promotes synthesis of a protein that stimulates cell cycle

• Mutations results in a ras oncogene, which codes for a hyperactive Ras protein, resulting in a protein that is active even in the absence of growth factor

• Hyperactive Ras protein continuously triggers kinase cascade, resulting in increased cell division

Tumour supressor genes

Encode for proteins that inhibit cell division by arresting the cell cycle at checkpoints, promote DNA repair and promote apoptosis (cell death)

Tumour supressor genes → mutated tumour supressor genes

Loss of function mutation

• Results in decrease in expression of normal gene product

• Is a recessive mutation, requires both alleles to be mutated

p53 tumour supressor gene

• codes for a protein that activates other genes which halts the cell cycle, allowing time for the cell to repair DNA

• p53 protein can also turn on genes directly involved in DNA repair and apoptosis (programmed cell death)

• If both copies of p53 gene in a cell mutates, defective p53 proteins are produced, hence cell cycle cannot be halted and DNA damage cannot be repaired

Types of tumours

Tumours: solid mass of cells from unregulated cell division

Benign: tumours that stay in one place

Malignant: tumours that invade surrounding tissues, may break away and start cancers elsewhere (metastasis)

Properties of cancer cells

1. Loss of contact inhibition: allows cells to proliferate and form a mass of cells called a tumour

2. Loss of anchorage dependence: allows cells to reduce adhesion to each other and travel to new locations

Development of cancer — accumulation of mutations

• At least one gain in function mutation (proto-oncogene → oncogene)

• Several loss of function mutations in tumour suppressor genes, allowing cells to continue dividing despite damage in DNA

• Activation of telomerase, where telomeres are lengthened and cell can divide infinitely

Development of cancer — angiogenesis

• Formation of new blood vessels, which are used to deliver nutrients (glucose, oxygen) to the tumour cells and enable them to spread to other sites in the body

• Cancer cells may promote angiogenesis by secreting growth factors (eg VEGF) that act on endothelial cells of surrounding blood vessels, stimulating them to proliferate and develop

Development of cancer — Metastasis

• Refers to spread of cancer cells to new locations in the body

• Invasion of surrounding tissues and vessels, migrate until they reach lymphatic vessels and are transported throughout the body

Causative factors of cancer

1. Genetic factors

   1. Inheritance of cancer-related mutations that increase the risk of cancer

2. Age

   1. Greater the age, the greater the accumulation of mutations in the body

3. Environmental factors

   1. Chemical carcinogens (eg tobacco, tar)

   2. Radiation (eg X-rays, UV radiation) that distort DNA’s double helix

4. Loss of immunity w infectious agents

   1. Failure of immune system to detect and remove cancer cells

   2. HIV can lead to higher risk of Kaposi sarcoma through weakening immune system

   3. Bacterium Helicobacter pylori produces toxin that controls cell growth, triggering stomach cancer