Malignant transformation
Under a malignant transformation is defined as the transition from normal, controlled in their growth cells to uncontrollably growing tumor cells . This transformation can be initiated, for example, under the influence of chemical substances or by so-called transforming (oncogenic) viruses such as the Rous sarcoma virus or SV40 . The process of malignant transformation is of great importance in understanding how cancer develops .
Transformation in cell culture
The term malignant transformation is now also used for the conversion of normal cells into cancer cells in an organism, although it was originally only used for the changes in cells in a cell culture in vitro . Transformed cells in a cell culture show all the characteristics of tumor cells such as uncontrolled growth, changes in cell contacts , growth in so-called soft agar ( cell culture medium with a proportion of 0.5 to 1% agar ) and formation of tumors after injection of the cells into animals.
In the case of a culture of adherent normal cells, that is to say adhering to the surface, the further growth of the cells is inhibited by contact with neighboring cells, so that usually only a single layer of cells ( monolayer ) is formed. In the case of a transformation, this inhibition does not take place and the clones derived from a transformed cell continue to divide and layer one another in several layers. This can be seen with the naked eye from the formation of cell densities, the so-called foci (plural of focus ). The malignant transformed cells also change their morphology and lose typical features of the original cell types (dedifferentiation).
Normal NIH-3T3 cells in a cell culture, phase contrast microscope 100 × magnification
Same cell culture after expression of the ras proto-oncogene : malignant transformation, beginning to develop a focus
Same cell culture after expression of the large T antigen from SV40: Malignant transformation with focus
Transforming Factors
Malignant transformation was first described as an effect in cell cultures that were infected with certain virus species. Since individual proteins of these viruses could also induce transformation on their own when introduced into cells, these proteins were referred to as transformation proteins. The genes for these transformation proteins are the viral oncogenes . The best-known transformation protein is the "large T antigen" ( T for transformation) of the SV40 virus, in which transformation was first discovered. Other proteins are the E1A protein of the human adenovirus (type 12, 18) and the E7 protein of the Papillomaviridae .
The intracellular parasite Theileria annulata secretes the peptidyl prolyl isomerase PIN1 , which transforms mammalian cells by breaking down the ubiquitin ligase FBW7 , since c-JUN is more active as a result .
swell
- Rolf Knippers: Molecular Genetics , 7th edition 1997
- Alfred Pühler et al. (Ed.): Lexicon of Biochemistry and Molecular Biology , Stuttgart 2000
Individual evidence
- ↑ J. Marsolier, M. Perichon, JD DeBarry, BO Villoutreix, J. Chluba, T. Lopez, C. Garrido, XZ Zhou, KP Lu, L. Fritsch, S. Ait-Si-Ali, M. Mhadhbi, S. Medjkane, JB Weitzman: Theileria parasites secrete a prolyl isomerase to maintain host leukocyte transformation. In: Nature. 520, 2015, p. 378, doi : 10.1038 / nature14044 .