An oncogene is a gene that promotes cell division. Normal cells divide according to the cell cycle, a controlled process that coordinates cell growth and multiplication in living tissue.
After a cell divides, it enters the interphase stage during which it can either prepare for a new division or stop dividing.
Oncogenes are defective or mutated genes that drive cell division even when it is not needed.
Proto Oncogenes and Normal Cells
In a normal cell, oncogene precursors called proto oncogenes control cell growth while suppressor genes keep cells from dividing when growth is not needed. Depending on the cell, proto oncogenes are either active and the cell divides, or switched off and the cell stops dividing. For processes such as growth or tissue-damage repair, cells have to divide rapidly, and the proto oncogenes need to be active.
Cells such as brain cells are highly specialized and don't divide. In these cells the proto oncogenes are switched off.
Sometimes a proto oncogene is damaged or its DNA is replicated incorrectly. Such mutations may switch it on permanently or may change it so that it drives cell division more intensively. These changed genes become oncogenes, and under certain conditions, they help cause runaway cell growth, resulting in tumors and cancer.
In addition to the presence of oncogenes, additional factors are necessary for cancer, but oncogenes are one of the root causes.
Normal Cell Division
In the cell cycle, normal cells divide during mitosis and then pass into the interphase stage. During interphase, cells either prepare for another division or enter the G0 phase in which they stop dividing.
If the cell is to divide, it goes through another cell cycle and produces two identical daughter cells. Normal proto oncogenes are active and keep the cell dividing.
This kind of cell division is important for replacing cells that have died and for the growth of young organisms. For example, skin cells are constantly dividing and replacing the cells in the outer skin layers. The cells of babies divide rapidly and allow the baby to grow into an adult. The proto oncogenes react to signals that say new cells or more cells are needed, and they keep the cells dividing to meet the signaled need.
Oncogenes and Cell Division
As the cell completes a cell cycle, it passes through three control points. At these points, the condition of the cell is assessed. If everything is proceeding normally, the cell division process continues. If there is a problem, such as incorrect DNA or insufficient cell material for two new cells, the process stops.
Oncogenes disrupt the operation of these control points. To interrupt the cell cycle, proto oncogenes may become deactivated or a suppressor gene may take over. If a proto oncogene has mutated into an oncogene, it may tell the cell to continue dividing despite the problems. The result can be a mass of defective cells.
Oncogenes, DNA Damage and Cell Death
A particularly important control point comes at the end of the interphase before the cell starts dividing in the mitosis phase. At this point, the cell checks to make sure the DNA has been completely duplicated and that there are no errors in the DNA strands. Typical errors are breaks in the DNA or incorrectly replicated genes.
If there is DNA damage, the corresponding proto oncogenes should be de-activated and the cell should stop the division process as it tries to repair its DNA. If an oncogene is present, it can help the cell ignore the stop signals and continue dividing.
The new cells will have faulty DNA and will not be able to function properly. In some cases cell growth will continue, and the daughter cells will form a tumor.
Sometimes the checks at the control point find that cell DNA damage is too severe to repair. In this case the cell is supposed to die off in a process called apoptosis. When oncogenes are present, they can help the cell bypass apoptosis and continue dividing. The new cells inherit the defective DNA as well as the oncogenes and can continue dividing in unlimited cell growth.
Oncogenes and Tumor Growth
When oncogenes help cells divide despite the presence of stop signals, the cells can grow into a small tumor very quickly. Such tumors are not dangerous by themselves because they don't have an independent blood supply, and tumor cells can't migrate and invade neighboring tissues. Tumor growth and cell migration causing metastasis require additional factors to proceed.
In addition to proto oncogenes that help regulate cell growth, cells also have tumor suppressor genes that limit the uncontrolled division of cells and the unnecessary growth of blood vessels. Developing a blood supply for growing tissue is called angiogenesis.
Both proto oncogenes and tumor suppressor genes control angiogenesis and make sure it doesn't support unlimited cell growth. When proto oncogenes mutate into oncogenes, they disrupt the effects of the tumor suppressor genes while they promote angiogenesis. The tumor can then grow larger with its own blood supply.
Sometimes oncogenes not only promote cell growth but also activate certain cell functions. For metastasis to take place, cells have to migrate through blood vessels to new sites and start multiplying there. Oncogenes can activate cell migratory behavior.
Now the tumor can become dangerous and may produce cancerous growth because it has its own blood supply, and the tumor cells can migrate through the new blood vessels.
Examples of Oncogenes
- TRK: The tropomyosin receptor kinase gene regulates cell behavior in the nervous system. When the corresponding oncogene is activated, it affects cell growth and mobility. These effects can contribute to cancer growth.
- RAS: The RAS family of proteins activates genes that control cell growth, differentiation and survival throughout the body. The corresponding oncogenes switch the RAS protein activation on permanently, leading to uncontrolled cell growth.
- ERK: The extracellular signal–regulated kinases help control cell mitosis and cell functions at the beginning of the interphase. The corresponding oncogenes help cells with DNA replication and sometimes work together with RAS oncogenes.
- MYC: The MYC gene family are proto octogenes that regulate DNA-to-RNA transcription. When activated as oncogenes, they turn on many genes including those that promote cell growth, and they can contribute to tumor formation.
The Formation of Cancerous Tumors
The formation of oncogenes from mutated proto oncogenes is just one factor in the formation of malignant cancerous tumors. Different oncogenes have to work together to promote cell growth and the formation of new tumor blood vessels.
Tumor suppressor genes have to either be switched off or they may themselves mutate to a form where they promote the growth of tumors. Finally, the natural cell death or apoptosis of cells with damaged DNA has to be overcome.
When all these factors come together, oncogenes first help defective cells grow into small tumors. They then promote the formation of blood vessels through angiogenesis and allow the tumor to grow further. At this point the cancer is still localized and has not spread to neighboring tissue or through the blood vessels.
For malignant cancer to develop, tumor cells have their migration function switched on by the corresponding oncogenes. Now tumor cells can migrate into adjacent tissue and metastasize throughout the body to produce new tumors. At that stage, the oncogenes have helped produce a case of malignant cancer.
The Occurrence of Human Cancer
Human oncogenes can cause cancer through the mutation of normal genes. Common cancers include lung cancer, breast cancer, colorectal cancer and cancer of the prostate gland. Human cancer cells spread via cell proliferation while cancer therapy tries to contain tumor growth and metastasizing through chemotherapy and radiation treatment.
Cancer research is focused on personalizing treatment to kill the particular cancer cells of the patient's tumor. Studying the molecular biology at the cancer cell level and looking at how gene expression leads to the cancer of each individual patient permits the customization of treatment specific to the patient's cancer and the reduction of side effects.
As a result of these treatment strategies, human cancer mortality rates have fallen even while human cancers become more common.
About the Author
Bert Markgraf is a freelance writer with a strong science and engineering background. He has written for scientific publications such as the HVDC Newsletter and the Energy and Automation Journal. Online he has written extensively on science-related topics in math, physics, chemistry and biology and has been published on sites such as Digital Landing and Reference.com He holds a Bachelor of Science degree from McGill University.