Absence of proximal duct apoptosis in the ventral prostate of transgenic mice carrying the C3(I)-TGF-β type II dominant negative receptor

BACKGROUND. Prostatic epithelial cells are sensitive to the inhibitory effects of TGF-β. However, TGF-β signaling in the prostate is dependent on androgenic status. Under the in vivo conditions, it is difficult to dissociate the effect of TGF-β from that of androgen on the prostate. METHODS. The objective of the present study was to create and verify a transgenic mouse system in which epithelial cells of the ventral prostate are insensitive to the actions of TGF-β. By using a modified prostate-specific promoter, C3(1), the TGF-β dominant negative receptor is only expressed in the epithelial cells of the ventral prostate, and these cells are resistant to TGF-β. Morphology of transgenic animal prostates was compared to wild- type animal prostates by immunohistochemistry and microscopy. RESULTS. The prostate of transgenic mice exhibited an abnormal morphology with multiple layers of epithelial cells lining the proximal ducts, in contrast to the simple cuboidal monolayer of cells seen in the normal prostate. This observation was accompanied by a loss of apoptosis in this region, as seen by TUNEL assay. There was no significant difference in serum levels of testosterone between the wild-type and transgenic animals. CONCLUSIONS. These results demonstrated that a loss of sensitivity to TGF-β results in the accumulation of multiple layers of epithelial cells in the proximal region of the ventral prostate. This abnormal growth illustrates that TGF-β plays an important role in regulating prostate growth. The current transgenic system can be used as an experimental model to study the functional role of TGF-β in prostatic growth and function. (C) 2000 Wiley-Liss, Inc.