Oncogene

An oncogene is a modified genethat increases the malignancy of a tumorcell. Some oncogenes, usually involved in early stages of cancer development, increase the chance that a normal celldevelops into a tumorcell, possibly resulting in cancer. New research indicates that small RNAs 21-25 nucleotides in length called miRNAscan control expression of these genes by upregulating them.

The first oncogene was discovered in 1982 by Robert Weinberg, a founding member of Whitehead Institutefor Biomedical Research and professor of biology at Massachusetts Institute of Technology.

Proto-oncogene

A proto-oncogene is a normal gene that can become an oncogene, either after mutation or increased expression. They code for proteinsthat help to regulate cell growthand differentiation. Proto-oncogenes are often involved in signal transductionand execution of mitogenicsignals, usually through its proteinproduct. Upon activation, it (or its product) becomes a tumor inducing agent, an oncogene.

Activation

The proto-oncogene can become an oncogene by a relatively small modification of its original function. There are two basic activation types:

• A mutationwithin 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 aberrationduring cell division. A distinct aberration in a dividing stem cellin the bone marrowleads 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, or mitogens, are usually secretedby 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.

Protein kinasesand related proteins

There are six known classes of protein kinases and related proteins that can become an oncogene:

1. 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 factorreceptor (VEGFR).
2. Cytoplasmic tyrosine kinases like the Src-family, Syk-ZAP-70family and BTKfamily of tyrosine kinases.
3. Regulatory GTPases, for example, the Ras protein.
4. Cytoplasmic Serine/Threoninekinases and their regulatory subunits, for example, the Raf kinase, and cyclin-dependent kinases(through overexpression).
5. Adaptor proteinsin signal transduction.
6. Transcription factors.

See also

• Tumor suppressor gene
• Apoptosis

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It uses material from the http://en.wikipedia.org/wiki/Oncogene Wikipedia article Oncogene.