STUDIES ON HUMAN PROSTATE TISSUE CONFORMATION AND INTER-CELLULAR REGULATORY SYSTEM

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A system endocrine factor, androgen, turns on the switch of the local control system of the prostate gland to induce development and proliferation. The aim of the present project was to investigage how the local factors were related to the changes of the prostate gland provoked by the manipulation of the endocrine environment of the prostate. Being supplied with the grant from 1997 to 1998, we conducted studies on the following markers of the local control system.1. Prostate epithelial function (prostate specific antigen ; PSA) : Immunohistochemical PSA stain in the prostate gland both in BPH and cancer, was weakened in patients undergoing androgen blockade treatments in whom serum PSA levels were decreased.2. Factors related to proliferation (c-erb-2, ki-67) : Immunohistochemical stain of ki-67 antigen in the prostate was also decreased in general in patients with androgen blockade treatment, but not in these with androgen blockade resistant or poorly differentiated cancer. We could not obtain definitive results on c-erb-2.3. Apoptosis (intranuclear DNA fragmentation) and apoptosis inhibitor (bcl-2) : Apoptosis was localized in the acinar epithelial cells, while bcl-2 was detected in the duct epithelial cells and basal cells. Apoptosis increased following androgen blockade treatments both in BPH and cancer tissue. Bcl-2, however, differentially expressed from apoptosis. In rats, apoptosis reached maximum 3 days aftercastration and thereafter decreased gradually. Expression of bcl-2 was delayd compared to apoptosis and increased gradually.Now, we are planning to extend our studies covering negative growth control factors such as TGF-beta, and more detailed relation to tissue conformation.