Oncogene

An oncogene is a gene that causes a cell to develop into a tumor cell.

Table of contents

1 Protooncogene 1.1 Activation 2 Oncogene 2.2 Growth factors 2.3 Protein kinases

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 a doubled amount of protein in the cell

Oncogene

Growth factors

Growth factors are usually secreted by 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 neighbouring cells.

Protein kinases

There are six known classes of tyrosine kinases that can become an oncogene:

1. Receptor tyrosine kinases that become constitutive (permanently) active.
2. Cytoplasmic tyrosine kinases, often products of viral oncogenes.
3. Regulatory GTPases, for example, the Ras protein.
4. Cytoplasmic Serine/Threonine kinases and their regulatory subunits, for example, the Raf kinase, and cyclines (through overexpression).
5. Adaptor proteins in signal transduction.
6. Transcription factors.