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


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.
Lin
M F
MF
Department of Biochemistry, College of Medicine, University of Nebraska Medical Center and Omaha Veterans Administration Medical Center, Omaha, Nebraska, USA.
Lee
M S
MS
Zhou
X W
XW
Andressen
J C
JC
Meng
T C
TC
Johansson
S L
SL
West
W W
WW
Taylor
R J
RJ
Anderson
J R
JR
Lin
F F
FF
D000135:Acid Phosphatase; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D010766:Phosphorylation; D011467:Prostate / Q000166:cytology / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000201:enzymology*; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D014183:Transplantation, Heterologous
D000135:Acid Phosphatase; D000728:Androgens; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases; D018719:Erb-b2 Receptor Tyrosine Kinases; C428439:prostatic acid phosphatase