Our research objectives are to understand the molecular basis for abnormal prostate growth. It is an inescapable fact that the majority of the aging male population will develop a benign and/or malignant prostate neoplasm during their lifetime. Our laboratory is presently studying alterations in gene expression that occur at the onset of prostate carcinogenesis. Expression profiling of microdissected prostate tissue using mRNA differential display and cDNA array analysis has led to the identification of several prostate growth related (PGR) genes. Thus far we have characterized one of these genes in detail, the B-cell translocation gene 2 (BTG2). We have made antibodies to the BTG2 protein product and have shown it to be expressed in a lesion suspected of predisposing to prostate cancer precursor but not in prostate cancer. The BTG2 protein functions as a tumor suppressor causing G1 arrest by indirectly regulating transcription (cyclin D1 is transcriptionally repressed target) and by modulating the activity of a protein arginine methyltransferase (see Figure). Our available data suggests that BTG2 fulfils a cytoprotective function in prostate cells as a 'growth brake' in response to cellular stress and growth stimuli and that BTG2 represents the earliest known tumor suppressor function lost at the onset of prostate carcinogenesis.

Another aspect of our work focuses on the involvement of the sympathetic nervous system in development of benign and malignant prostate neoplasms. We are investigating the mechanism of prostate neoplasia that occurs in animal models with elevated sympathetic activity. We anticipate that our research will further the understanding of the pathogenesis of prostate neoplasia that will ultimately aid in the development of alternative therapeutic modalities for benign prostatic hyperplasia and prostate cancer.