Editing Oncogene (section)

=== 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, or within a regulatory region (for example the promoter region), can cause a change in the protein structure, causing
#* an increase in protein ([[enzyme]]) activity
#* a loss of [[Regulation of gene expression|regulation]]
# An increase in the amount of a certain protein (protein concentration), caused by
#* an increase of protein expression (through misregulation)
#* an increase of protein (mRNA) stability, prolonging its existence and thus its activity in the cell
#* [[gene duplication]] (one type of [[Chromosome abnormalities|chromosome abnormality]]), resulting in an increased amount of protein in the cell
# 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 a 2nd gene (this 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}}</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.