Cell Enzyme May Act as Tumor Suppressor

An enzyme that normally alters the activity of other protein molecules in cells may also help suppress tumors, according to a new study.

The enzyme is known as PTPRO (protein tyrosine phosphatase receptor-type O), and when the gene responsible for producing PTPRO is silenced, as can occur in lung cancer, for instance, the amount of enzyme decreases, allowing the cells to grow when they should not. The study, conducted by investigators at The Ohio State University Comprehensive Cancer Center (Columbus, OH, USA), may provide a new target for cancer therapy, lead to new methods to diagnose some cancers, and determine a patient's prognosis and response to treatment.

"This appears to be the first report of an enzyme also serving as a tumor suppressor. It shouldn't come as a surprise, however, because of the nature of this enzyme,” said Dr. Samson T. Jacob, professor of molecular and cellular biochemistry and internal medicine at Ohio State.

PTPRO removes phosphate groups from the amino acid tyrosine found in certain proteins. Some proteins become activated and some become inactivated when phosphate groups are removed. It is probable that the silencing of PTPRO changes the phosphate levels of some of these proteins and helps start mechanisms that lead to cancer.

The investigators demonstrated that the PTPRO gene is slowly silenced by methylation, which causes the addition of small chemical units known as methyl groups to a gene. As the methyl units gather on a gene, the gene becomes less active and fewer copies of its protein are produced. In this instance, silencing of the PTPRO gene results in a decrease in the level of the PTPRO enzyme. That, in turn, affects specific proteins that PTPRO acts on, advancing the progression of cancer. The scientists studied the PTPRO gene for methylation in 43 primary human lung tumors and their matching normal neighboring tissue. Fifty-one percent of the tumor samples were very methylated, whereas the gene in the neighboring normal tissue was fundamentally methylation-free.

When the investigators altered laboratory-grown human lung cancer cells to overproduce the PTPRO enzyme, they demonstrated that the cells grew more slowly and more frequently died from programmed cell death--apoptosis. In addition, when the scientists used a chemical to remove the methylation in a cancer-cell line, it slowed the growth of the cells, once more suggesting that the presence of the PTPRO gene and its enzyme suppressed the cancer process.

Combined, the results strongly suggest that the PTPRO gene is a tumor-suppressor gene. If additional studies validate the significance of the PTPRO gene to the cancer process, it may mean that assessing the amount of methylation of this gene in a tumor will tell physicians something about the degree of danger posed by the tumor or whether the tumor is responding well to treatment. The researchers are now trying to identify the proteins that the PTPRO enzyme interacts with, and they are studying samples from a wide variety of cancers to learn which ones also show silencing of the PTPRO gene.