Stable lower PAR expression decreased DU145 prostate cancer cell growth inSCID mice

BACKGROUND. PAR is a novel gene ubiquitously expressed in normal and malign ant tissues with a trend towards higher expression in tumor cells. PAR biol ogical function is unknown. Here we report the effect of lowering PAR expre ssion on in vitro and in vivo proliferation of DU145 cells. METHODS. Decreased PAR expression was achieved by stable transfection of DU 145 cells with antisense PAR cDNA cloned in pCMV-Script expression vector. The proliferative potential of DU145 transfectants was studied by cell coun ts, colony formation in soft agar, flow cytometry, and growth in severe com bined immunodeficient (SCID) mice. RESULTS. DU145 transfectants exhibited a decreased cell proliferation in ti ssue culture and a low efficiency of colony formation in soft agar. Flow cy tometry revealed an arrest of these cells in G2-M phase of mitotic cycle. A dramatic decrease of tumor growth was observed when DU145 transfectant cel ls were inoculated in SCID mice, compared with controls. Histological exami nation of these tumors showed a marked decrease in cell density and in numb er of mitoses while control tumors showed a high cell density and numerous mitoses. CONCLUSIONS. The data presented here provide the first evidence for PAR gen e cellular function and its possible implication in malignant transformatio n. (C) 2001 Wiley-Liss, Inc.