View source for Oncogene

== Proto-oncogene ==
A '''proto-oncogene''' is a normal gene that could become an oncogene due to mutations or increased [[Gene expression|expression]]. Proto-oncogenes code for [[protein]]s that help to regulate the [[cell growth]] and [[cell differentiation|differentiation]]. Proto-oncogenes are often involved in [[signal transduction]] and execution of [[mitosis|mitogenic]] signals, usually through their [[protein]] products. Upon acquiring an activating mutation, a proto-oncogene becomes a tumor-inducing agent, an oncogene.<ref>{{cite journal | vauthors = Todd R, Wong DT | title = Oncogenes | journal = Anticancer Research | volume = 19 | issue = 6A | pages = 4729–4746 | year = 1999 | pmid = 10697588 }}</ref> Examples of proto-oncogenes include [[Ras (protein)|RAS]], [[Wnt signaling pathway|WNT]], [[Myc|MYC]], [[Extracellular signal-regulated kinases|ERK]], and [[Trk receptor|TRK]]. The MYC gene is implicated in [[Burkitt's lymphoma]], which starts when a [[chromosomal translocation]] moves an [[enhancer sequence]] within the vicinity of the MYC gene. The MYC gene codes for widely used transcription factors. When the enhancer sequence is wrongly placed, these transcription factors are produced at much higher rates. Another example of an oncogene is the [[Bcr-Abl]] gene found on the [[Philadelphia chromosome]], a piece of genetic material seen in Chronic Myelogenous Leukemia caused by the translocation of pieces from chromosomes 9 and 22. Bcr-Abl codes for a tyrosine kinase, which is constitutively active, leading to uncontrolled cell proliferation. (More information about the Philadelphia Chromosome below)

=== Activation ===
[[Image:Ch1-oncogene.svg|right|thumb|From proto-oncogene to oncogene]]
The proto-oncogene can become an oncogene by a relatively small modification of its original function. There are three basic methods of activation:
#A [[mutation]] within a proto-oncogene can cause a change in the protein structure, causing
#* an increase in protein activity
# An increase in the amount of a certain protein (protein concentration), caused by
#* an increase of gene expression through mutations in the promoter region
#* an increase of protein stability, prolonging its existence and thus its activity in the cell
#* [[gene duplication]] (one type of [[Chromosome abnormalities|chromosome abnormality]])
# A [[chromosomal translocation]] (another type of [[Chromosome abnormalities|chromosome abnormality]])
#*There are 2 different types of chromosomal translocations that can occur:
##translocation events which relocate a proto-oncogene to a new chromosomal site that leads to higher expression
##translocation events that lead to a fusion between a proto-oncogene and another gene which creates a [[fusion protein]] with increased cancerous/oncogenic activity
##* the expression of a constitutively active ''hybrid protein''. This type of mutation in a dividing [[stem cell]] in the [[bone marrow]] leads to adult [[leukemia]]
##*Philadelphia Chromosome is an example of this type of translocation event.  This chromosome was discovered in 1960 by [[Peter Nowell]] and David Hungerford, and it is a fusion of parts of DNA from chromosome 22 and chromosome 9. The broken end of chromosome 22 contains the "BCR" gene, which fuses with a fragment of chromosome 9 that contains the "[[ABL (gene)|ABL1]]" gene.  When these two chromosome fragments fuse the genes also fuse creating a new gene: "BCR-ABL".  This fused gene encodes for a protein that displays high protein tyrosine kinase activity (this activity is due to the "ABL1" half of the protein). The unregulated expression of this protein activates other proteins that are involved in cell cycle and cell division which can cause a cell to grow and divide uncontrollably (the cell becomes cancerous).  As a result, the Philadelphia Chromosome is associated with Chronic Myelogenous Leukemia (as mentioned before) as well as other forms of Leukemia.<ref>{{cite journal| vauthors = Chial H |title=Proto-oncogenes to Oncogenes to Cancer|journal=Nature Education|year=2008|volume=1|issue=1|url=https://www.nature.com/scitable/topicpage/proto-oncogenes-to-oncogenes-to-cancer-883/|accessdate=25 June 2025}}</ref>

The expression of oncogenes can be regulated by [[microRNA]]s (miRNAs), small [[RNA]]s 21-25 nucleotides in length that control gene expression by [[downregulate|downregulating]] them.<ref name=Negrini>{{cite journal | vauthors = Negrini M, Ferracin M, Sabbioni S, Croce CM | title = MicroRNAs in human cancer: from research to therapy | journal = Journal of Cell Science | volume = 120 | issue = Pt 11 | pages = 1833–1840 | date = June 2007 | pmid = 17515481 | doi = 10.1242/jcs.03450 | doi-access = free }}</ref> Mutations in such [[microRNAs]] (known as [[oncomir]]s) can lead to activation of oncogenes.<ref name="Esquela-Kerscher">{{cite journal | vauthors = Esquela-Kerscher A, Slack FJ | title = Oncomirs - microRNAs with a role in cancer | journal = Nature Reviews. Cancer | volume = 6 | issue = 4 | pages = 259–269 | date = April 2006 | pmid = 16557279 | doi = 10.1038/nrc1840 | s2cid = 10620165 }}</ref> [[Antisense]] messenger RNAs could theoretically be used to block the effects of oncogenes.