Decreased expression of cellular prostatic acid phosphatase increases tumorigenicity of human prostate cancer cells

Purpose: Understanding cell proliferation regulation in hormone refractory prostate cancer may provide answers for novel solutions. Protein tyrosine p hosphatases have been thought to have key roles in regulating cell prolifer ation and be involved in oncogenesis, although to our knowledge their funct ional roles in human prostate cancer remain unknown. Human prostatic acid p hosphatase (PAcP), a major phosphatase in prostate epithelium, has been sho wn to function as a neutral protein tyrosine phosphatase in these cells. We evaluated the biological significance of cellular prostatic acid phosphata se expression in human prostate cancer cells. Materials and Methods: Immunohistochemical testing of human prostate cancer archival specimens was done to evaluate the expression of cellular PAcP. I mmunoprecipitation and immunoblotting were performed to determine cellular PAcP and SH2 domain-bearing tyrosine phosphatase-1 levels as well as tyrosi ne phosphorylation of c-ErbB-2/neu in different human prostate cancer cells . The biological behavior of LNCaP derivative sublines was characterized in vitro and in vivo by soft agar analysis and xenograft. animal inoculation. Results: Immunohistochemical staining of human prostate clearly showed that cellular levels of PAcP significantly decreases in prostate cancer cells ( p <0.001). The results of biochemical characterization revealed that the ce llular level of PAcP but not SHP-1, another differentiation associated prot ein tyrosine phosphatase, consistently correlated negatively with the growt h of several human prostate cancer cell lines. Reintroducing cellular PAcP activity in prostate cancer cells by PAcP complementary DNA transfection re sulted in decreased tyrosine phosphorylation of c-ErbB-2/neu, decreased pro liferation rates in culture as well as decreased anchorage independent grow th in soft agar. The xenograft. animal model demonstrated that a higher tum or growth rate as well as larger size is associated with a lower level of c ellular PAcP. Conclusions: Cellular PAcP can down-regulate prostate cancer cell growth, a t least partially by dephosphorylating c-ErbB-2/neu, Therefore, decreased c ellular PAcP expression in cancer cells may be involved in prostate cancer progression.