Cancer research with a “warm” result: Researchers have shown the potential of a notorious cancer gene for the regeneration of damaged hearts. Experiments in mice suggest that if this gene is activated specifically in the heart, it can trigger cell divisions in the tissue and allow new heart cells to grow back. The result thus offers starting points for the development of regenerative forms of treatment after heart attacks, say the scientists.
Once cardiac muscle cells have died, they no longer grow back – this lack of regeneration ability of our pumping gans becomes a problem, especially after infarcts: the blockage in a blood vessel leads to insufficient supply of the tissue and thus the death of many heart cells. In contrast to other organs in the body, the adult heart cannot replace the lost cardiomyocytes – instead, scarring forms. As a result, many patients suffer from reduced heart strength, which in the worst case can lead to failure of the pumping gans. This so-called heart failure affects millions of people worldwide – and so far there are no cures.
It would therefore be ideal if the heart muscle cells could be stimulated to divide – but so far this has not been possible. The extent to which cells are allowed to make copies of themselves is strictly controlled in the body and depends on the type of tissue. Disorders of this system are also life-threatening: when cells divide in an uncontrolled manner, begin to proliferate and spread through the body, they are called cancer. The cause is disturbances in the activity of certain hereditary systems. The Myc gene occupies a notorious position. It is involved in the regulation of dividing activity. It is known to be overactive in the cells of most cancers. That is why the Myc gene is currently the focus of cancer research. It is hoped to gain control over its activity to curb tumor tissue growth.
Why there is no heart cancer
Scientists led by Catherine Wilson from the University of Cambridge are also researching the Myc gene. To investigate its function, they have developed a genetically modified breeding line of mice in which the Myc gene has increased activity in the body. As was to be expected, there was an increased formation of cell growth in various organs in these animals. But the heart was not affected. The researchers have investigated why this is the case using methods of the so-called ChIP-Seq technology, which can show protein-DNA interactions.
As Wilson and her colleagues explain, the Myc gene is responsible for the formation of a so-called transcription factor. This protein binds to certain sections of DNA in cells and activates the reading of genes that are involved in the growth processes of the cells. The researchers were able to show that the protein also binds to the DNA in the heart cells of their experimental animals. Nevertheless, this did not activate the gene expression necessary for cell growth. Through further investigations, the scientists were able to show that the lack of another factor is responsible for this: the gene for the protein cyclin T1 is not active in heart cells. “We found that even when Myc is turned on in the heart, something is missing to ensure that it works. This could be one of the reasons heart cancer is so extremely rare, ”says Wilson.
Cardiac cells brought to division
In the next step, the researchers artificially increased the concentration of Cyclin T1. They achieved this through a genetic modification that led to the formation of cyclin T1 in the heart cells of the mice. Thus, this protein, together with Myc, was increasingly produced in the hearts of the experimental animals. As the researchers report, this had a resounding effect: the hearts went into a regenerative state – the cells divided. “When these two genes were overexpressed together in the cardiac muscle cells of adult mice, we saw extensive cell replication, which led to a sharp increase in the number of cardiac muscle cells,” says Wilson.
The findings are still far from being converted into a form of therapy, but the researchers now see the result as important fundamental potential: “None of the current treatment options can reverse the degeneration of the heart tissue. It is now becoming apparent what is missing so that hearts can regenerate themselves, ”said Wilson. She and her colleagues hope that their study can now help develop therapies for the treatment of heart disease.
According to them, genetic methods are also conceivable: short-term, switchable technologies could be used to specifically activate Myc and Cyclin T1 in the heart. “This could potentially prevent collateral damage that could lead to cancer in the body,” says the scientist. So it will be interesting to see what will develop from this interesting approach.
University of Cambridge, technical article: Nature Communications, doi: 10.1038 / s41467-020-15552-x