Enzyme becomes potential drug target
enzyme that normally alters the activity of other protein molecules
in cells may also help prevent lung cancer.
The enzyme represents a new drug target for cancer therapy and may lead to new ways to diagnose some cancers and determine a patient's prognosis and response to treatment.
Scientists discovered that when the gene responsible for producing the enzyme is silenced, as can happen in lung cancer, for example, the amount of the enzyme drops, allowing the cells to grow when they shouldn't.
Study leader Samson Jacob said: "This appears to be the first report of an enzyme also serving as a tumour suppressor although it shouldn't come as a surprise, however, because of the nature of this enzyme."
The enzyme, known as protein tyrosine phosphatase receptor-type O (PTPRO), removes phosphate groups from the amino-acid tyrosine found in specific proteins. Some proteins become activated and some become inactivated when phosphate groups are removed.
It is likely that the silencing of PTPRO alters the phosphate levels of some of these proteins and helps initiate processes that lead to cancer.
In this study, Jacob showed the PTPRO gene is silenced by a process known as methylation. This causes the addition of small chemical units known as methyl groups to a gene. As methyl units accumulate on a gene, fewer copies of its protein are made.
In silencing this PTPRO gene, the level of the PTPRO enzyme also decreased. This affects certain proteins that PTPRO acts on, furthering the cancer process. The gene is also known as a tumour-suppressor gene where normal activity of the gene suppresses cancer development.
In examining the PTPRO gene for methylation in 43 primary human lung tumours and their matching normal adjacent tissue. 51 per cent of the tumour samples were heavily methylated, while the gene in the adjacent normal tissue was essentially methylation-free.
When the researchers modified laboratory-grown human lung-cancer cells to over produce the PTPRO enzyme, they showed that the cells proliferated more slowly and more often died from apoptosis.
The evidence strongly suggests that if the research verifies the importance of the PTPRO gene to the cancer process, it may mean that measuring the degree of methylation of this gene in a patient's tumour will tell doctors something about the level of danger posed by that tumour or whether the tumour is responding well to treatment.
The team from The Ohio State University Comprehensive Cancer Centre, are now working to identify the proteins that the PTPRO enzyme interacts with and they are analysing samples from a wide range of cancers to learn which ones also show silencing of the PTPRO gene.
The World Health Organisation estimates that over 900,000 new cases of lung cancer were diagnosed worldwide in 2000. However, the incidence of lung cancer is not the same in all countries with some of the highest rates in New Zealand and the US and the lowest rates in India, Africa and South America.
Lung cancer is most commonly diagnosed in people in the age range of 55-65 years old. Although the incidence of lung cancer is now falling in men, it continues to rise in women.
