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.
- Michal Mlacki, Charbel Darido, Stephen M. Jane, Tomasz Wilanowski. Loss of Grainy Head-Like 1 Is Associated with Disruption of the Epidermal Barrier and Squamous Cell Carcinoma of the Skin. PLoS ONE, 2014; 9 (2): e89247 DOI: 10.1371/journal.pone.0089247
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