- Key People:
- Harold Varmus
- J. Michael Bishop
- Related Topics:
- gene
- tumor suppressor gene
- RAS oncogene
oncogene
-
What is an oncogene?
An oncogene is a segment of DNA that can cause cancer. It originates as a proto-oncogene, which encourages normal cell differentiation and proliferation. When a proto-oncogene mutates, through processes such as point mutation, translocation, or gene amplification, it can interfere with regular cell regulation, leading to uncontrolled cell growth and potentially cancerous tumors. Examples of oncogenes include c-ERBB2 (HER2), linked to breast cancer, and c-MYC, associated with lung cancer.
2 Britannica SourcesCreated from Britannica articles using AI. AI can make mistakes, so verify using Britannica articles. -
How do oncogenes differ from normal genes?
Oncogenes are genes that can cause cancer when mutated or altered. They originate from normal genes called proto-oncogenes, which regulate cell growth and division.
Proto-oncogenes encourage normal cell differentiation and proliferation, while oncogenes lead to uncontrolled cell growth and tumor formation. Proto-oncogenes can turn into oncogenes through point mutations, translocation, or amplification, which can result in deregulation and excess protein production, disrupting normal cell processes.
2 Britannica SourcesCreated from Britannica articles using AI. AI can make mistakes, so verify using Britannica articles. -
What role do oncogenes play in cell growth?
Oncogenes originate from proto-oncogenes, which are crucial for cell growth and differentiation. When a proto-oncogene mutates into an oncogene, it can disrupt normal cellular regulation, potentially leading to uncontrolled cell growth and tumor formation.
Proto-oncogenes can turn into oncogenes through point mutations, translocation, or gene amplification, all of which ultimately reduce cellular regulation. Researchers have linked specific oncogenes to particular cancers, such as the c-ERBB2 (HER2) oncogene in breast cancer and the c-MYC oncogene in lung cancer. The RAS gene family appears in 20% of all human cancers.
2 Britannica SourcesCreated from Britannica articles using AI. AI can make mistakes, so verify using Britannica articles. -
How can mutations turn a normal gene into an oncogene?
Proto-oncogenes, which encourage cell differentiation and proliferation, can mutate into oncogenes, leading to uncontrolled cell growth and potentially cancer.
Here's how mutations can turn a normal gene into an oncogene:
* Point Mutation A single alteration of a nucleotide base can arise spontaneously or from carcinogens or ultraviolet radiation. This mutation can change the amino acid sequence of the encoded protein, altering its function.
* Translocation A chromosome segment breaks off and attaches to another chromosome. If this segment contains a proto-oncogene, it loses its regulatory controls and is overproduced, disrupting normal cell processes.
* Gene Amplification The number of copies of the proto-oncogene increases, leading to overproduction of proteins that disrupt cellular processes.3 Britannica SourcesCreated from Britannica articles using AI. AI can make mistakes, so verify using Britannica articles. -
How are oncogenes connected to the development of cancer?
Oncogenes are mutated forms of proto-oncogenes, which normally regulate cell growth and division. Proto-oncogenes can turn into oncogenes through various mechanisms, including point mutations, chromosomal translocation, and gene amplification. These mutations can lead to the overproduction of proteins that stimulate cell division or disrupt the normal regulation of cell growth. The resulting uncontrolled cell growth can lead to the development of cancerous tumors. For example, the RAS oncogene, found in many human cancers, has a single defect that causes it to constantly send activation signals, leading to uncontrolled cell proliferation.
3 Britannica SourcesCreated from Britannica articles using AI. AI can make mistakes, so verify using Britannica articles. -
What are some ways scientists study and target oncogenes in cancer treatment?
Oncogenes, mutated from proto-oncogenes, can cause uncontrolled cell growth and tumors. Scientists study oncogenes to develop targeted therapies that interfere with molecules responsible for tumor cell behavior, blocking cancer growth and spread.
Two main types of targeted therapies are:
* Monoclonal antibodies These target the surface of tumor cells.
* Small-molecule drugs These affect targets inside the cell.One of the first targeted therapies was trastuzumab (Herceptin) for breast cancer, which occupies estrogen receptors on the surface of breast cancer cells, suppressing their growth stimulus. Another drug, Imatinib, inhibits an abnormal protein in leukemia cells, controlling the disease without disturbing normal cells.
These therapies embody personalized medicine, treating specific defects in a patient’s tumor.
4 Britannica SourcesCreated from Britannica articles using AI. AI can make mistakes, so verify using Britannica articles.
oncogene, genetic material that carries the ability to induce cancer. An oncogene is a sequence of deoxyribonucleic acid (DNA) that has been altered or mutated from its original form, the proto-oncogene. Operating as a positive growth regulator, the proto-oncogene is involved in promoting the differentiation and proliferation of normal cells. A variety of proto-oncogenes are involved in different crucial steps of cell growth, and a change in the proto-oncogene’s sequence or in the amount of protein it produces can interfere with its normal role in cellular regulation. Uncontrolled cell growth, or neoplastic transformation, can ensue, ultimately resulting in the formation of a cancerous tumor.
Oncogenes first were discovered in certain retroviruses (viruses composed of RNA instead of DNA and that contain reverse transcriptase) and were identified as cancer-causing agents in many animals. In the mid-1970s, the American microbiologists John Michael Bishop and Harold Varmus tested the theory that healthy body cells contain dormant viral oncogenes that, when triggered, cause cancer. They showed that oncogenes are actually derived from normal genes (proto-oncogenes) present in the body cells of their host.
With DNA sequences similar, but not identical, to their viral equivalents, proto-oncogenes occur naturally within the genomes of a wide variety of vertebrate species, including humans, but do not cause cellular transformation. Although a useful function of the proto-oncogene was not initially apparent, and it was believed to be “silent” or not expressed until being “switched on” to cause uncontrolled growth, its importance in cell regulation was soon identified.
" height="20" alt="HEW Logo">
The similarity between viral and cellular oncogenes can be explained by the life strategy of the retrovirus. The virus inserts itself into the genome of the host cell in order to replicate and then removes itself to infect other cells, sometimes capturing a portion of the host cell’s genome along with its own. If a proto-oncogene has been integrated into a virus’ own genetic material, its proper regulation may not be possible given the limited genetic repertoire of the retrovirus and it is transformed into an oncogene.
The term proto-oncogene was coined to distinguish the normal gene from its altered form. The resulting nomenclature is somewhat misleading. Onco-, from the Greek onkos, meaning “bulk,” or “mass,” refers to the tumor-causing ability of the oncogene, which is apt, but the term proto-oncogene stresses the potential the gene has to become a malignant force, rather than its integral role as a regulator of cell activity.
Oncogenes, as with all other genes, are often designated by abbreviations (e.g., MYC and RAS). The origin or location of the gene is indicated by the prefix of “v-” for virus or “c-” for cell or chromosome; additional prefixes, suffixes, and superscripts provide further delineation. More than 70 human oncogenes have been identified. Breast cancer has been linked to the c-ERBB2 (HER2) oncogene and lung cancer to the c-MYC oncogene. Oncogenes arising in members of the RAS gene family are found in 20 percent of all human cancers, including lung, colon, and pancreatic.
In humans, proto-oncogenes can be transformed into oncogenes in three ways, all of which result in a loss of or reduction in cell regulation. An alteration of a single nucleotide base pair, called a point mutation, can arise spontaneously or as a result of environmental influences such as chemical carcinogens or ultraviolet radiation. This seemingly minor event can lead to the production of an altered protein that cannot be properly regulated. Point mutations are responsible for converting certain RAS proto-oncogenes to oncogenes. A second method of oncogenesis occurs by the process of translocation, in which a segment of the chromosome breaks off and attaches to another chromosome. If the dislocated chromosome contains a proto-oncogene, it may be removed from its regulatory controls and be continuously produced. The excess production of protein molecules disrupts the cellular process normally under their control, thereby destabilizing the delicate balance of the mechanisms of cell growth.
The trusted destination for professionals, college students, and lifelong learners.
SUBSCRIBE
Many leukemias and lymphomas are caused by translocations of proto-oncogenes. The third method of transformation involves an amplification in the number of copies of the proto-oncogene, which also can result in overproduction of the protein and its concomitant effects. Amplified proto-oncogenes have been found in tumors from patients with breast cancer and neuroblastoma (a tumor of the sympathetic nervous system that affects young children).