Expression of senescence-associate beta-galactosidase in enlarged prostates from men with benign prostatic hyperplasia

Objectives. Cellular senescence is a unique cellular response pathway thoug ht to be closely associated with the aging process. The senescent phenotype is characterized by the loss of a cell's ability to respond to proliferati ve and apoptotic stimuli even while normal metabolic activity and vitality is maintained. Recently, a novel biomarker, senescent-associated beta-galac tosidase (SA-beta-gal), was found to identify cells with the senescent phen otype. In the present study, we examined whether human prostatic epithelial cells adopt a senescence-associated phenotype after prolonged culture and analyzed a series of human benign prostatic hyperplasia (BPH) specimens to determine whether the cellular senescence process might be a factor in the development of BPH. Methods. A primary culture of epithelial cells was established from the nor mal tissue of the peripheral zone of a radical prostatectomy specimen and w as serially passaged until senescence. Forty-three human prostate specimens were obtained subsequent to radical prostatectomy or transrectal ultrasoun d-guided biopsy. The cultured cells and tissue specimens were histochemical ly stained to reveal the expression of SA-beta-gal, the cellular senescence biomarker. Results. As has been reported for other types of cultured cells, human pros tatic epithelial cells demonstrated widespread expression of the cellular s enescence marker, SA-beta-gal, on prolonged culture. In our survey of hyper trophied human prostate tissues, 17 specimens (40%) of the 43 analyzed demo nstrated positive staining for SA-beta-gal. In these tissues, SA-beta-gal e xpression was noted only in the epithelial cells. No statistical correlatio n (P = 0.42) between the chronologic age of the patient donor and SA-beta-g al expression was found. However, a high prostate weight (greater than 55 g ) was found to correlate strongly with the expression of the SA-beta-gal bi omarker (P = 0.0001). Conclusions. Cultured prostatic epithelial cells expressed SA-beta-gal on r eaching replicative senescence in vitro. The survey of human BPH specimens for the senescent marker showed that prostatic epithelial cells in patients with BPH with more advanced enlargement of the prostate (greater than 55 g prostate weight) expressed SA-beta-gal, and the prostates from patients wi th BPH that weighed less than 55 g tended to lack senescent epithelial cell s. On the basis of these results, we propose that the accumulation of senes cent epithelial cells may play a role in the development of the prostatic e nlargement associated with BPH. UROLOGY 56: 160-166, 2000. (C) 2000, Elsevi er Science Inc.