Research Project
2715085
Glutathione S-transferase-pi (GST-pi) is one of the enzymes responsible for removing endogenous and exogenous toxins from the body, and as such it is commonly found in most cells. Expression of this enzyme has been found to change dramatically in many cancers. While in most cancers the protein is over-expressed compared to normal tissue and is associated with resistance to chemotherapy, it is almost universally absent in prostate cancer. In prostate cancer, the mechanism for this change in protein expression has been found to be methylation of the promoter region of the gene. Methylation of the promoter region of genes prevents transcription into their functional protein, and methylation of key regulatory genes such as p15, p16, and E-cadherin, has been found in many cancer types. We propose development of a simple-to-use DNA amplification assay for GST-pi methylation. We will the use this assay to analyze a set of prostate cancer patients with known tumor marker status and long term survival data, as well as a group of normal and benign condition controls. This data will be analyzed to determine the diagnostic and prognostic potential of a GST-pi methylation assay alone and in conjunction with other known prostate cancer risk factors such as elevated serum prostate specific antigen, tumor size and grade. PROPOSED COMMERCIAL APPLICATIONS: The most common screening methods used today for early detection are digital rectal exam and serum PSA, however both methods have a high rate of false positives, and neither are very good at differentiating between benign prostatic hyperplasia (BPH) and prostatic cancer. Differentiation of these 2 conditions currently requires subjecting the patient to biopsy. We believe that methylation of the GST-pi gene may be a more specific characteristic of prostate cancer than elevated serum PSA, and may offer a better way to segment the at-risk, PSA positive population prior to or after biopsy.
