By Sally Robertson
There are trillions of living cells in the body that grow, divide, and die in an orderly fashion. This process is tightly regulated by the genes within a cell’s nucleus. These genes code for proteins that help regulate cell growth. These important genes are called proto-oncogenes. A change in the DNA sequence of the proto-oncogene gives rise to an oncogene, which produces a different protein and interferes with normal cell regulation.
Proto-oncogenes have many functions in a cell but they often code for proteins that stimulate cell division, prevent cell differentiation or regulate programmed cell death (apoptosis). These are all essential processes required for normal growth, development and the maintenance of healthy organs and tissues. However, a mutated or defective version of a proto-oncogene (oncogene) increases the production of these proteins, thereby leading to unregulated cell division, a slower rate of cell differentiation and increased inhibition of cell death. Together, these features define cells that have become cancerous.
Currently, researchers are aware of more than 40 different types of proto-oncogenes in humans. Several genetic mechanisms that cause a proto-oncogene to become an oncogene have also been elucidated and examples are given below:
- Point mutations, insertions or deletions that give rise to an overactive gene product
- Point mutations, insertions or deletions that lead to an increase in transcription
- Gene amplification leading to additional copies of a proto-oncogene
- Chromosomal translocation that causes a proto-oncogene to move to a different chromosomal site associated with increased expression
- Chromosomal translocations that cause a proto-oncogene to fuse with another gene to produce a protein that has oncogenic activity.
Research into oncogenes has improved understanding and knowledge about why certain individuals are more susceptible to cancer than others. Some people are more likely to have their proto-oncogenes converted to oncogenes and develop cancer. The agents that cause cancer such as radiation, viruses and environmental toxins, for example, are more likely to cause cancer in these individuals.
One example of a well known proto-oncogene is the HER2 gene. This gene codes for a transmembrane tyrosine kinase receptor called human epidermal growth factor receptor 2. This protein receptor is involved in the growth, repair and division of cells in the breast. In a healthy breast cell, there are two copies of HER2, but in some types of breast cancer, the cells contain more than 2 copies, which lead to an excess production of the HER2 protein. This causes the breast cells to grow, divide and proliferate much more quickly than healthy breast cells.
This genetic defect in the breast cells is not inherited but is most likely to arise as a result of aging. Researchers are still investigating whether environmental factors such as smoke and pollution increase the likelihood of the defect occurring.
If a woman is diagnosed as HER2 positive, she has an abnormal number of HER2 genes and is producing too much of the HER2 protein. This means cells in her breast are growing in an upregulated manner and forming a cancerous tumor. If a woman is diagnosed as HER2 negative, then it is not HER2 protein production that is causing the cancer.
Another example of a proto-oncogene is the Myc gene, which codes for transcription factors. When the gene sequence of Myc is altered, these transcription factors are produced at increased rates and gene expression is altered giving rise to the formation of a tumor.
Last Updated: Dec 22, 2014