Jan 14, 2000. Boston/ PSA Rising/ -- Researchers at Beth Israel Deaconess Medical Center have discovered a new protein in human prostate tissue that may play an important role in cancer. The protein, called "PDEF," may lead to new treatments and to a better understanding of the biology of the disease. Prostate cancer has become the most frequent solid cancer in older men and is the second leading cause of cancer deaths in men.

PDEF is a transcription factor, a protein that takes the first step in gene expression by making a working copy of the DNA template. It belongs to a family of transcription factors (the ets family) that is thought to be involved in other cancers. PDEF, however, appears to be different, according to a paper by immunologist Towia Libermann, Ph.D., and his colleagues in the Jan. 14 issue of the Journal of Biological Chemistry.

Unlike its siblings, which are scattered throughout more cells in the body, PDEF is found mostly in the prostate epithelium, the cells lining the prostate that give rise to cancer. That means researchers could theoretically snip out the tiny region of the gene that turns it on in the prostate and attach it to genes that fight cancer.

"Higher doses of therapeutic agents could be delivered specifically to the prostate cancer, which would spare other tissues and thus may result in fewer side effects," Libermann says.

So far, the direct role of PDEF in prostate cancer is unclear, but if PDEF is critical to the biology of prostate cancer, it could even become a new target, rather than a vehicle, for future treatment efforts.

Other evidence in the recent paper suggests that PDEF may provide an important clue in the puzzling transformation from early stage prostate cancer, which can be treated by drugs that suppress male hormones, to the advanced stage, which grows independently of hormones and is associated with metastasis and death.

According to the paper, PDEF triggered expression of the gene that makes "prostate-specific antigen" (PSA), which is measured in blood tests to diagnose or monitor prostate cancer (although PSA can also indicate other prostate or kidney disorders). In tissue cultures, PDEF enhanced hormone-triggered PSA expression (in cooperation with androgen receptors) but surprisingly also turned on PSA gene expression independently of male hormones. Strengthening the PDEF-cancer connection, preliminary data from follow-up studies by Libermann and his colleagues suggests that PDEF may be expressed in higher levels in more advanced cancers.

The research was conducted in collaboration with scientists at Human Genome Sciences of Rockville, Md., which has applied for a patent on the PDEF gene. The research was funded by CaP CURE and the National Institute of Health. An abstract of the research article is online

J Biol Chem 2000 Jan 14;275(2):1216-25 PDEF, a novel prostate epithelium-specific ets transcription factor, interacts with the androgen receptor and activates prostate-specific antigen gene expression. Oettgen P, Finger E, Sun Z, Akbarali Y, Thamrongsak U, Boltax J, Grall F, Dube A, Weiss A, Brown L, Quinn G, Kas K, Endress G, Kunsch C, Libermann TA New England Baptist Bone and Joint Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.