Making Proteins To Fight Cancer

An approach to treating intestine cancer is being developed by Russian researchers from the Bioengineering Centre, Russian Academy of Sciences, under Anna Prokhorchuk’s guidance jointly with American colleagues sponsored by the international CRDF foundation and the Federal Agency for Science and Innovation (Rosnauka).

Any cancerous disease changes the genetic landscape – some genes are suppressed, others get activated, which results in tumour growth, the formation of metastases, and cancer spreads beyond immune system control. The universal mechanism which regulates genes’ activity is DNA methylation, where a methyl group is joined to a certain section of a molecule. Special methyl-DNA binding proteins come into action, bound with a section of the methylated DNA and this suppresses gene activity. The researchers are interested in one of such proteins named Kaiso. They assume that this protein plays an important role in the intestine cancer development, and it can be used for diagnostics and treatment.

First, the researchers measured the level of expression of the Kaiso protein gene in intestinal tumours in mice and in human patients. The level of expression turned out to be dozens of times higher than that in healthy organs and tissues. ‘Kaiso-zero’ mice were then used which were found to be resistant to cancer. The same resistance to cancer was acquired by mice whose DNA methylation had been suppressed by other methods.

As the Kaiso protein content in the majority of human tumours is much higher than that in healthy tissues, it can be potentially used for early detection of cancer. Contemporary molecular methods allow to analyze expression of dozens of genes in the cancerous growth tissues and to compare the obtained picture with the “gene portrait” of normal cells. Certainly, the Kaiso gene is not the only one that can be used for such diagnosticums. The tumour represents a very heterogeneous and rather dynamic system, which requires knowledge of almost the entire “genetic portrait” of 28,000 genes.

It is thought that there are other between 10 and 30 key genes which can also serve as markers of tumour characteristics. This will save resources and time, relieving the necessity of analyzing the entire multithousand genome.

In cancer therapy, chimeric Kaiso protein could be created. The ordinary Kaiso protein (via DNA methylated binding) inhibits the work of cancer suppressor genes. However, it is possible, using the same properties of the protein, to make it not suppress, but reinforce the work of these genes. This is what the researchers are striving to achieve. “Although, there are hidden pitfalls here,” explains Anna Prokhorchuk, project manager. “It is necessary to make chimeric Kaiso work only to activate cancer suppressor genes, not the other methylated DNA sequences. This is what we are working at in the Bioengineering Centre jointly with American colleagues.” The ultimate aim of the investigation is to scrutinize the possibility for using Kaiso protein as a target for directional anticancer therapy.