Oncogene
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An oncogene is a gene that can cause a cell to develop into a tumor cell, possibly resulting in cancer.
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Protooncogene
A protooncogene is a gene that is involved in signal transduction and execution of mitogenic signals, usually through its protein product. Upon activation, it (or its product) becomes a tumor inducing agent, an oncogene.
Activation
The protooncogene can become an oncogene by a relatively small modification of its original function. There are two basic activation types:
- A mutation within a protooncogene can cause a change in the protein structure, caused by
- 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
Oncogene
Growth factors
Growth factors are usually secreted by a few special cells to induce cell proliferation in other cells. 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.
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).
- Cytoplasmic tyrosine kinases like the Src-family, Syk-ZAP-70 family and BTK family of tyrosine kinases.
- 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.
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