8.4: Oncogenes
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 \(\PageIndex{2}\).
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 \(\PageIndex{1}\)
All human cells have proto-oncogenes. True or False?
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True.
Exercise \(\PageIndex{2}\)
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
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Dr. Todd Nickle and Isabelle Barrette-Ng (Mount Royal University) The content on this page is licensed under CC SA 3.0 licensing guidelines.