8.4: Oncogenes
- Last updated
- Jan 9, 2023
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- Page ID
- 102526
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The control of cell division involves many different genes. Some of these genes act as signaling molecules to activate normal progression through the cell cycle. One of the pre-requisites for cancer occurs when one or more of these activators of cell division become mutated.
The mutation may involve a change in the coding sequence of the protein, so that it is more active than normal, or a change in the regulation of its expression, so that it is produced at higher levels than normal, or persists in the cell longer than normal. Genes that are a part of the normal regulation of cell division, but which after mutation contribute to cancer, are called proto-oncogenes. Once a proto-oncogene has been abnormally activated by mutation, it is called an oncogene. More than 100 genes have been defined as proto-oncogenes. These include genes at almost every step of the signaling pathways that normally induce cell to divide, including growth factors, receptors, signal transducers, and transcription factors.

The ras oncogene was originally identified from cancer-causing viruses. ras is an example of a proto-oncogene; this protein acts as a transducer in signal transduction pathways, including the regulation of cell division. When a receptor protein receives a signal for cell division, the receptor activates ras, which in turn activates other signaling components, ultimately leading to activation of genes involved in cell division. Certain mutations of the ras sequence causes it to be in a permanently active form, which can lead to constitutive activation of the cell cycle. This mutation is dominant as are most oncogenes. An example of the role of ras in relaying a signal for cell division in the EGF pathway is shown in Figure 8.4.2.

Ras mutations in cancer
There are three ras homologs in the human genome (HRas, NRas, and KRas). As many cancer genomes are sequenced, databases such as COSMIC (http://www.sanger.ac.uk/cosmic) can be used to search mutations across cancer types.
Visit the site and search for HRAS, NRAS, or KRAS. Can you find answers to these questions?
- What amino acid positions are frequently mutated?
- In what cancer types is the gene most often mutated?
- Are the mutations most often missense, nonsense, frameshift, or silent? Is this what you would have predicted -- why or why not?
Exercise 8.4.1
All human cells have proto-oncogenes. True or False?
- Answer
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True.
Exercise 8.4.2
Are the mutations that convert proto-oncogenes to oncogenes like to be loss-of-function or gain-of-function mutations? Explain your reasoning.
- Answer
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Oncogenic mutations are typically gain-of-function, resulting in increased protein activity and therefore increased cell proliferation.
A loss-of-function mutation in a proto-oncogene, would result in reduced cell proliferation, not cancer.
Contributors and Attributions
Dr. Todd Nickle and Isabelle Barrette-Ng (Mount Royal University) The content on this page is licensed under CC SA 3.0 licensing guidelines.