The family of transforming growth factors betas (TGF-bs) comprises pleiotropic molecules involved in growth inhibition, stress-induced premature senescence, epithelial mesenchymal transition and lumenal differentiation. The aim of this study was to clarify the effect of long time exposure of TGF-bs- which can be found in high concentrations in seminal fluid and areas of benign prostatic hyperplasia (BPH)- to human prostate basal cells. Basal cell cultures established from prostate explants either underwent cellular senescence (30 population doublings), or were stimulated with TGF- beta 1, 2 and 3 for one or six days. Quite similar to cellular senescence, TGF-bs stimulation resulted in an increase of SA-beta galactosidase (SA-b-gal) activity, cyclin-dependent kinase inhibitors p21CIP1 gene expression and down-regulation of the inhibitor of differentiation Id-1. But most other genes induced by cellular senescence in prostate epithelial cells, such as p16INK4A, IFI-6-16, Dkk-3 or Pai-1 were unaffected. Interestingly, cells stained positive for the lumial cytokeratins 8/18, but did not express other lumenal markers, such as prostate specific antigen and androgen-receptors. TGF-bs increased the expression of the mesenchymal marker vimentin, indicating that basal epithelial cells underwent differentiation with lumenal and mesenchymal features and not cellular senescence. Furthermore, in vitro differentiated neuroendocrine-like cells, expressing chromogranin A and cytokeratin 18 strongly stained positive for SA-b-gal. Thus, it is concluded, that SA-b-gal activity is not only a marker specific for senescence, but also for differentiation of human prostate epithelial cells.