Protooncogenes

Protooncogenes are genes that code for proteins responsible for proliferation. If a mutation occurs in protooncogene, there is an increase in protein expression, hyperactivity and loss of regulation. This mutated form is called oncogene.

Another mechanism leading to tumor proliferation is a mutation of antiproliferative tumor-suppressor genes. Usually, both copies of tumor-suppressor gene have to be mutated so the effect is manifested (two-hit hypothesis). Protooncogenes, however, differ in that area – mutation of one copy of the protooncogene to oncogene is often sufficient.

Protooncogenes can encode a wide variety of proteins with multiple functions (cell differentiation genes, signaling molecules, surface receptors, regulatory genes, ...). If there is damage to signaling pathways e.g proteins, it may alter the reactivity of cells to the action of growth factors and significantly increase cell division. This may be caused by several mechanisms:
 * protein begins to be formed in cells in which they normally do not form;
 * protein is made in appropriate cells, but in excessive amounts;
 * protein is formed in a form that can not be regulated by normal mechanisms.

Currently, about 40 genes are known to be protooncogenes. In 16 of them direct correlation with tumor proliferation was shown, such as:
 * Her-2/neu: breast cancer;
 * K-ras: tumors of the eosophagus, colon, pancreas;
 * beta-Catenin: Pancreatic cancer;
 * Cyclin E: liver tumors;
 * mutant B-Raf: melanomas.

Examples of (proto) oncogenes
Among oncogenes include forms derived growth factor PDGF, receptors of growth hormones or proteins, intracellular signaling pathways. All these cells are characterized by similar behavior – responding as if they constantly receive instructions for signaling division. The cells are so completely beyond regulatory control.

Among oncogenes include the viral src gene. Viruses that cause cancer are called transformation viruses (often it is a retrovirus). Normally, the src protein kinase regulates genes controlling cell division. Individual structures of oncogene and protooncogene differ in several amino acids.

Viral oncogenes – normal function protooncogene – tumors caused by mutations:
 * abl oncogene – Tyr-specific protein kinase – pre-B-lymphocytic leukemia;
 * crest-B – epidermal growth factor (EGF) – erythroleukemia;
 * fos, jun – gene regulation – osteosarcomas, fibrosarcomas;
 * myc – regulation of gene expression – sarcomas and carcinomas;
 * src – Tyr-specific protein kinase – sarcomas.

Related articles

 * Mutation