Protooncogenes

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

Another mechanism of tumor proliferation is a mutation of antiproliferative tumor-suppressor genes. They always occur in the genome in two copies, and their damage is the intervention of both copies. Protooncogenes, however, differs in that area – mutation of one copy of the protooncogene to oncogene is enough of a speech (the dominant character).

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

New research links appeared relationship between the activation of protooncogenes to oncogenes through microRNAs. MicroRNAs are parts of RNA which have size of 21-25 nucleotides. They can control the expression of these genes with their down-regulation. In the future they could possibly be used to block the activity of oncogenes.

Currently, 40 species are known to be protooncogenes. In 16 of them were proven direct correlation with tumor proliferation, 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 for 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