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

被引:58
作者
Lin, MF
Lee, MS
Zhou, XW
Andressen, JC
Meng, TC
Johansson, SL
West, WW
Taylor, RJ
Anderson, JR
Lin, FF
机构
[1] Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA
[2] Univ Nebraska, Med Ctr, Dept Urol Surg, Omaha, NE 68198 USA
[3] Univ Nebraska, Med Ctr, Dept Pathol, Omaha, NE 68198 USA
[4] Univ Nebraska, Med Ctr, Coll Med, Dept Prevent & Societal Med, Omaha, NE 68198 USA
[5] Univ Nebraska, Med Ctr, Eppley Canc Inst, Omaha, NE 68198 USA
[6] Omaha Vet Adm, Med Ctr, Omaha, NE USA
关键词
prostate; prostatic neoplasms; disease progression; protein-tyrosine-phosphatase;
D O I
10.1016/S0022-5347(05)65725-4
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose: Understanding cell proliferation regulation in hormone refractory prostate cancer may provide answers for novel solutions. Protein tyrosine phosphatases have been thought to have key roles in regulating cell proliferation and be involved in oncogenesis, although to our knowledge their functional roles in human prostate cancer remain unknown. Human prostatic acid phosphatase (PAcP), a major phosphatase in prostate epithelium, has been shown to function as a neutral protein tyrosine phosphatase in these cells. We evaluated the biological significance of cellular prostatic acid phosphatase 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. Immunoprecipitation and immunoblotting were performed to determine cellular PAcP and SH2 domain-bearing tyrosine phosphatase-1 levels as well as tyrosine 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 cellular level of PAcP but not SHP-1, another differentiation associated protein tyrosine phosphatase, consistently correlated negatively with the growth of several human prostate cancer cell lines. Reintroducing cellular PAcP activity in prostate cancer cells by PAcP complementary DNA transfection resulted in decreased tyrosine phosphorylation of c-ErbB-2/neu, decreased proliferation rates in culture as well as decreased anchorage independent growth in soft agar. The xenograft. animal model demonstrated that a higher tumor growth rate as well as larger size is associated with a lower level of cellular PAcP. Conclusions: Cellular PAcP can down-regulate prostate cancer cell growth, at least partially by dephosphorylating c-ErbB-2/neu, Therefore, decreased cellular PAcP expression in cancer cells may be involved in prostate cancer progression.
引用
收藏
页码:1943 / 1950
页数:8
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