Oncogene

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An oncogene is a gene that is responsible for the normal growth and differentiation of cells. This is demonstrated by their high degree of evolutionary conservation.[1] In tumour cells, they are often mutated or expressed at high levels.[2]

Many abnormal cells normally undergo a programmed form of death (apoptosis). Activated oncogenes can cause those cells to survive and proliferate instead.[3] Most oncogenes require an additional step, such as mutations in another gene, or environmental factors, such as viral infection, to cause cancer. Since the 1970s, dozens of oncogenes have been identified in human cancer. Many cancer drugs target those DNA sequences and their products.[2][4][5][6]

Contents

Proto-oncogene

A proto-oncogene is a normal gene that can become an oncogene due to mutations or increased expression. The resultant protein may be termed an oncoprotein.[7] 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.[8] Examples of proto-oncogenes include RAS, WNT, MYC, ERK, and TRK.

Activation

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

  • A mutation within a proto-oncogene can cause a change in the protein structure, causing
  • An increase in 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
    • a gene duplication (one type of chromosome abnormality), resulting in an increased amount of protein in the cell
  • A chromosomal translocation (another type of chromosome abnormality), causing
    • an increased gene expression in the wrong cell type or at wrong times
    • the expression of a constitutively active hybrid protein. This type of aberration in a dividing stem cell in the bone marrow leads to adult leukemia

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