P&S Journal: Fall 1995, Vol.15, No.3
Clincal Advances: By Lynne Christensen
Prostate Cancer: Oncogene Identified
Researchers in pathology and urology have identified a human prostatic carcinoma oncogene (PTI-1), paving the way for development of an improved diagnostic test for early detection of prostate cancer. Depending on the results of future studies, PTI-1 may be used to develop cancer therapeutics as well.
According to the American Cancer Society, about 244,000 American men will be diagnosed with prostate cancer in 1995, 40,500 of whom will likely die of the disease. Early detection is the key to reducing the mortality rate. Unfortunately, current methods for detecting prostate cancer are neither highly sensitive nor highly specific. Physical examination may miss small or centrally located tumors; serum prostate-specific antigen (PSA) determination detects both malignant and benign prostate disease; and sampling error in tissue biopsy may lead to erroneous benign diagnosis.
Using a novel gene discovery technology, a team headed by Dr. Paul B. Fisher, professor of clinical
pathology, the Chernow Research Scientist in Pathology and Urology, and director of the neuro-oncology program at CPMC, found the PTI-1 gene to be a member of a class of oncogenes that may affect protein translation fidelity and contribute to carcinoma development in human prostate tissues and perhaps in other types of cancer.
The identification method involved isolating DNA from human prostate cancer cells, cotransfecting it into CREF-Trans 6 cells, and injecting them into nude mice. Using a technique called differential RNA display (DD), researchers then isolated the gene in the tumor-derived cells that displayed increased expression. In this case, they identified PTI-1.
Once the gene was found, researchers tested whether it would be expressed in prostate cancer tissue, tissue from prostates with benign hypertro-phy, and normal prostate tissue. They discovered that it was expressed only in the cancerous tissue. This specificity means the gene could potentially serve as the basis of a diagnostic test that would be preferable to the current PSA test, which cannot differentiate between benign enlargement of the prostate and prostate cancer.
Dr. Fisher and his colleagues also analyzed PTI-1 expression in cell lines associated with other forms of cancer and found PTI-1 expression was evident in human carcinomas in the lung, breast, and colon. PTI-1 expression was not detected in human melanoma, neuroblastoma, osteosarcoma, normal cerebellum, or glioblastoma multiforme cell lines.
Just as important as the discovery of the particular gene is the refinement of the technique used to find it. The use of rapid expression cloning with the CREF-Trans 6 system and the differential RNA display strategy can be applied to identify and clone other human oncogenes.