Oncogene
Oncogenes (literally cancer genes ) are parts of the genetic makeup of a cell which , if excessively activated, promote the transition from the normal growth behavior of the cell to unchecked tumor growth. The “gene” in oncogene is not used here, as in the words carcinogenic or mutagenic , in the sense of “generating” or “promoting”, but is derived directly from the word gene as part of the genetic make-up.
Oncogenes play an important regulating role in normal cell growth , cell division and cell differentiation . The excessive, unphysiological and tumorigenic activation of an oncogene occurs either through a constitutively activating mutation from the wild-type allele of an oncogene or through excessive expression (upregulation) of the mRNA of the wild-type oncogene and its protein.
Proto-oncogenes
The wild-type alleles of the oncogenes are commonly referred to as proto- oncogenes in cell biology . By a constitutively activating gain-of-function - mutation of the genomic DNA of an oncogene results from the wild-type allele, a constitutively activated allele actual oncogene in cell biological functional sense. These mutations can be caused by harmful physical influences ( UV radiation , ionizing radiation ), chemical substances ( carcinogens , mutagens ), biological agents (for example viruses ), but they can also occur randomly (i.e. stochastically ).
Classifications
More than 100 oncogenes are known today (as of 2004). All cell cycle control genes are potential oncogenes, since their change or dysfunction can mean the loss of control over cell division.
Oncogenes are divided into several groups based on the proteins they encode :
- Growth factors
- Growth factor receptors
- G proteins , for example encoded by the Ras proto-oncogenes
- Non-receptor protein kinases , for example tyrosine kinases , serine / threonine kinases
- nuclear transcription factors
- tumor-specific chromosomal aberrations
- constitutively activated oncogenes from viruses such as tax, the oncogene of HTLV-1 , HTLV-2 and the bovine leukosis virus ( BLV ).
Oncogenes occur - in their non-activated wild-type form - in every cell and encode proteins that control and regulate the growth, division and differentiation of a cell. Many components that affect the growth of a cell can be viewed as oncogenes. If such a gene mutates, there is in most cases a loss of function, cell division is no longer promoted, and the cell can no longer divide. This usually results in programmed cell death, known as apoptosis , which is not a problem for the organism, as there are normally enough other divisible cells in the vicinity.
But there is also the possibility that the constitutively activating mutation of the oncogene promotes cell division. It can happen that chromosome rearrangements cause a growth gene to come under the influence of a promoter , which normally has a strong activating effect. For example, the immunoglobulin promoters are able to activate oncogenes and thus contribute to the development of tumors.