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The new tumor suppressor gene will facilitate the detection of people susceptible to skin cancer
24 February 2014
Nencki Institute of Experimental Biology
One of the mouse genes displays strong suppressive properties against the development of non-melanoma skin cancers, which was proven by a team of Polish and Australian researchers. The experimental results are a promising step towards more effective prophylactic tests and new methods of treatment of this type of tumors in human patients.
The human genome contains approximately 20,000 protein coding genes which are responsible for the formation, development and functioning of the human body. A similar number of genes exists in the mouse genome. In this pool only some genes – called tumor suppressors – can initiate the production of proteins having anti-cancer properties. Polish-Australian team of researchers from the Nencki Institute of Experimental Biology of the Polish Academy of Sciences in Warsaw .and Monash University Central Clinical School in Melbourne showed that one of the genes, known as GRHL1, displays anti-cancer effects which is protective against skin cancer of non-melanoma type.
“In humans, we know more than 700 tumor suppressor genes, but only a few of them prevent the development of skin cancer. We have identified yet another tumor suppressor gene, whose damage certainly increases the risk of skin cancer, at least in a mouse model”, says Dr. Tomasz Wilanowski from the Nencki Institute.
Cancer is currently one of the deadliest and most common diseases. According to statistical data from the World Health Organization, annually more than 8 million people die of cancer worldwide. Therefore understanding the causes of this disease and development of effective methods of prevention and therapy of cancer are of great social importance.
In 1998, Dr. Wilanowski identified, cloned and described a new human gene. GRHL1 (Grainyhead-like 1) proved to be a factor co-responsible for 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 that we conducted recently in our laboratory, leave no doubt. In the control mice, severe skin cancers developed in 7% of the population. In knockout mice, that is, in mice lacking the functional GRHL1 gene, such tumors appeared in as many as 33% of cases”, says PhD student Michal Mlacki of the Nencki Institute, lead author of the paper that was just published in a well-known scientific journal PLOS ONE.
Researchers from the Nencki Institute emphasize that these numbers cannot be automatically applied to the human population. “Although mouse and human 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 Michal Mlacki.
“Today we cannot yet unequivocally answer the question whether people with a defective GRHL1 gene will be five times more likely to develop non-melanoma skin cancer, as it happens in mice, or whether the risk of this disease will increase fourfold, or sixfold. Studies on the determination of the scale of the increased risk in human population have only just begun”, notes Dr. Wilanowski.
Finding of a new tumor suppressor gene is the first step towards the development of tests to detect defective GRHL1 gene in children and adults. In the future, people aware of their genetic defect could take preventive measures to reduce the risk of skin cancer, for example, by avoiding tanning salons, suitably dressing on a sunny day or using creams effectively blocking ultraviolet radiation.
“Gene itself is only the vehicle of information. It is the encoded protein that is responsible for 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”, says Dr. Wilanowski.
Studies on new tumor suppressor gene were funded by the National Science Centre of Poland, the European Molecular Biology Organization and Seventh Framework Programme of the European Union.
The Nencki Institute of Experimental Biology of the Polish Academy of Sciences has been established in 1918 and is the largest non-university centre for biological research in Poland. Priority fields for the Institute include neurobiology, neurophysiology, cellular biology and biochemistry and molecular biology – at the level of complexity from tissue organisms through cellular organelles to proteins and genes. There are 31 labs at the Institute, among them modern Laboratory of Confocal Microscopy, Laboratory of Cytometry, Laboratory of Electron Microscopy, Behavioural and Electrophysiological Tests. The Institute is equipped with state-of-the-art research equipment and modernized animal house, where lab animals are bred, also transgenic animals, in accordance with the highest standards. Quality of experiments, publications and close ties with the international science community, place the Institute among the leading biological research centres in Europe.
One of the genes discovered in the Nencki Institute of Experimental Biology in Warsaw, has strong tumor suppressive properties in non-melanoma skin cancers. (Source: Nencki Institute, Grzegorz Krzyżewski)
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