Oncogenes Double Whammy
Pancreatic cancer is an aggressive tumor of glandular tissue, which ranks first in terms of mortality among all oncological diseases.
Researchers have long been searching for factors that explain aggressive growth and early metastasis of pancreatic cancer.
A group of researchers from the Technical University of Munich and the German Cancer Consortium demonstrated the connection of tumor aggressiveness with specific gene amplification occurring during the evolution of cancer. Based on this information, they deduced the basic principles underlying the development of cancer.
Healthy human cells contain two copies of each gene. The researchers produced a mutation in one of the copies of the KRAS gene in mice. This gene plays an important role in cell proliferation and is activated in 90% of human pancreatic cancer. The common name of such genes is oncogenes. The researchers made an amazing discovery: the mutated gene was duplicated even in the earliest stages of cancer. In cases where the mutant KRAS gene was not duplicated, doubling of other oncogenes was detected.
Thus, cancer cells enhance growth due to the presence of additional copies of genes. Such gene amplification has not previously been considered as a cause of aggressive growth and early metastasis of pancreatic cancer.
As a rule, healthy cells have a mechanism of protection against the accumulation of mutations. How were oncogenes able to double, bypassing the cell's own defenses?
After the mutation of the KRAS gene induced by the researchers, a mutation occurred in a group of genes that are tumor suppressors. A healthy cell contains a whole series of such genes that protect against the development of cancer. The conclusion of the researchers is that the strengthening of the KRAS gene or other oncogenes occurs as a result of a violation of the function of one or another "protective" gene.
After disabling the protective mechanisms of the cell, oncogenes are amplified, leading to rapid tumor growth. Which oncogene and to what extent it has intensified – this largely determines the characteristics of the tumor, the features of the course and prognosis of pancreatic cancer.
The mouse model of amplification helped to identify genetic patterns that explain the aggressiveness and rate of cancer metastasis. The authors emphasize that the results of the study can be projected onto other types of cancer. The next step is a more in–depth study of the genetic mechanisms of tumor progression and the development of new methods for treating pancreatic cancer using the information obtained in the study.
Article by Sebastian Mueller et al. Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes published in the journal Nature.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the Technical University of Munich: Insights into cancer evolution.