New Tumor Suppressor Gene Found
April 29, 2014
A team of Polish and Australian researchers have pinpointed a mouse gene that can suppress the development of non-melanoma skin cancers.
The experimental results are a promising step toward more effective prophylactic tests and new methods of treatment of this type of tumor in human patients.
The human genome contains approximately 20,000 protein coding genes that are responsible for the formation, development and functioning of the human body. A similar number of genes exists in the mouse genome. Only some genes—called tumor suppressors—can initiate the production of proteins with anti-cancer properties. A Polish-Australian team of researchers from the Nencki Institute of Experimental Biology of the Polish Academy of Sciences in Warsaw and the Monash University Central Clinical School in Melbourne showed that one of the genes, known as GRHL1, displays anti-cancer effects protecting patients against non-melanoma skin cancer.
“In humans, we know of more than 700 tumor suppressor genes, but only a few of them prevent the development of skin cancer,” says Dr. Tomasz Wilanowski from the Nencki Institute. “We have identified yet another tumor suppressor gene which, if damaged, clearly increases the risk of skin cancer, at least in mice.”
Cancer is currently one of the deadliest and most common diseases. According to the World Health Organization, annually more than 8 million people die of cancer worldwide. Understanding the causes of this disease and developing effective methods of prevention and treatment are of special importance.
In 1998, Wilanowski identified and cloned a new human gene. The GRHL1 (Grainyhead-like 1) turned out to play a role in the formation of the largest human organ: the skin. This allowed the Polish-Australian research team to carry out experiments on the influence of this gene on the incidence of skin cancer.
“The tests leave no doubt. In the control mice, severe skin cancers developed in 7 percent of the population. In mice lacking the functional GRHL1 gene, such tumors appeared in as many as 33 percent of cases,” says Michał Mlącki, a doctoral student at the Nencki Institute.
Researchers from the Nencki Institute say these numbers cannot be automatically assumed to be the same in the human population. “Although mice and humans are very similar in terms of genetics and physiology, they are still different organisms. Mice are only research models of human disorders and facilitate better understanding of disease processes,” says Mlącki.
Wilanowski said, “Today we cannot yet unequivocally say whether people with a defective GRHL1 gene will be five times more likely to develop non-melanoma skin cancer, as happens in mice, or whether the risk of this disease will increase fourfold, or sixfold. Studies to determine the scale of the increased risk in the human population have only just begun.”
Finding a new tumor suppressor gene is the first step toward developing tests to detect a defective GRHL1 gene in children and adults. In the future, people aware they have a genetic defect could take preventive measures to reduce the risk of skin cancer, for example by avoiding tanning salons, dressing appropriately on a sunny day or using creams effectively blocking ultraviolet radiation.
“A gene itself is only a carrier of information,” says Wilanowski. “It is the encoded protein that is responsible for the anti-cancer effect of the GRHL1 gene. Now that we know the functions of this protein, we would like to find a way to stimulate its activity in the human body. And this is the way not only to prevention, but also to future drugs that can be administered to patients.”
Research on the new tumor suppressor gene has been financed by Poland’s National Science Center, the European Molecular Biology Organization and the European Union under its 7th Framework Program.