Oncogene
From Wikipedia, the free encyclopedia
An oncogene is a modified gene, or a set of nucleotides that codes for a protein, that increases the malignancy of a tumor cell. Some oncogenes, usually involved in early stages of cancer development, increase the chance that a normal cell develops into a tumor cell, possibly resulting in cancer. New research indicates that small RNAs 21-25 nucleotides in length called miRNAs can control expression of these genes by downregulating them.
The first oncogene was discovered in 1970 and was termed SRC (pronounced SARK). Src was in fact first discovered as an oncogene in a chicken retrovirus. Experiments performed by Dr G. Steve Martin of the University of California, Berkeley demonstrated that the SRC was indeed the oncogene of the virus. In 1976 Drs. J. Michael Bishop and Harold E. Varmus of the University of California, San Francisco demonstrated that oncogenes were defective proto-oncogenes, found in many organisms including humans. For this discovery Bishop and Varmus were awarded the Nobel Prize in 1989.
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[edit] Proto-oncogene
A proto-oncogene is a normal gene that can become an oncogene, either after mutation or increased expression. Proto-oncogenes code for proteins that help to regulate cell growth and differentiation. Proto-oncogenes are often involved in signal transduction and execution of mitogenic signals, usually through their protein products. Upon activation, a proto-oncogene (or its product) becomes a tumor inducing agent, an oncogene.
[edit] Activation
The proto-oncogene can become an oncogene by a relatively small modification of its original function. There are two basic activation types:
- A mutation within a proto-oncogene can cause a change in the protein structure, causing
- an increase in protein (enzyme) activity
- a loss of regulation
- the creation of a hybrid protein, through a chromosomal aberration during cell division. A distinct aberration in a dividing stem cell in the bone marrow leads to adult leukemia
- An increase in protein concentration, caused by
- an increase of protein expression (through misregulation)
- an increase of protein stability, prolonging its existence and thus its activity in the cell
- a gene duplication, resulting in an increased amount of protein in the cell
[edit] Oncogene
[edit] Growth factors
Growth factors, or mitogens, are usually secreted by a few specialized cells to induce cell proliferation in paracrine, autocrine, or endocrine manner. If a cell that usually does not produce growth factors suddenly starts to do so (because it developed an oncogene), it will thereby induce its own uncontrolled proliferation (autocrine loop), as well as the proliferation of neighboring cells. In addition, abnormal growth of endocrine glands often cause ectopic production of growth hormones that have secondary effects on other parts of the body.
[edit] Protein kinases and related proteins
There are six known classes of protein kinases and related proteins that can become an oncogene:
- Receptor tyrosine kinases that become constitutively (permanently) active like the epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR). For example, HER2/neu.
- Cytoplasmic tyrosine kinases like the Src-family, Syk-ZAP-70 family and BTK family of tyrosine kinases. For example, the Abl gene in CML - Philadelphia_chromosome.
- Regulatory GTPases: for example, the Ras protein.
- Cytoplasmic Serine/Threonine kinases and their regulatory subunits: for example, the Raf kinase, and cyclin-dependent kinases (through overexpression).
- Adaptor proteins in signal transduction.
- Transcription factors: for example the myc gene.
