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

BACKGROUND. Prostatic epithelial cells are sensitive to the inhibitory effe cts of TGF-beta. However, TGF-beta signaling in the prostate is dependent o n androgenic status. Under the in vivo conditions, it is difficult to disso ciate the effect of TGF-beta from that of androgen on the prostate. METHODS, The objective of the present study was to create and verify a tran sgenic mouse system in which epithelial cells of the ventral prostate are i nsensitive to the actions of TGF-beta. By using a modified prostate-specifi c promoter, C3(1), the TGF-beta dominant negative receptor is only expresse d in the epithelial cells of the ventral prostate, and these cells are resi stant to TGF-beta. Morphology of transgenic animal prostates was compared t o wild-typo animal prostates by immunohistochemistry and microscopy. RESULTS. The prostate of transgenic mice exhibited an abnormal morphology w ith multiple layers of epithelial cells lining the proximal ducts, in contr ast 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-b eta results in the accumulation of multiple lavers of epithelial cells in t he proximal region of the ventral prostate. This abnormal growth Illustrate s that TGF-beta 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-beta in prostatic growth and function. (C) 2000 Wil ey-Liss, Inc.