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1 Research Center for Molecular Endocrinology and WHO Collaborating Centre, Biocenter Oulu, University of Oulu; Departments of 2 Surgery, Division of Urology, and 3 Pathology, Oulu University Hospital, Oulu, Finland; 4 Department of Biological and Environmental Sciences, Division of Biochemistry, and 5 Institute of Biotechnology, Electron Microscopy Unit, University of Helsinki, Helsinki, Finland
Requests for reprints: Pirkko T. Vihko, Department of Biological and Environmental Sciences, Division of Biochemistry, FI-00014 University of Helsinki, Helsinki, Finland. Phone: 358-40-543-1734; Fax: 358-9-1915-9694; E-mail: pirkko.vihko{at}helsinki.fi.
Prostatic acid phosphatase (PAP) is currently evaluated as a target for vaccine immunotherapy of prostate cancer. This is based on the previous knowledge about secretory PAP and its high prostatic expression. We describe a novel PAP spliced variant mRNA encoding a type I transmembrane (TM) protein with the extracellular NH2-terminal phosphatase activity and the COOH-terminal lysosomal targeting signal (Yxx
). TM-PAP is widely expressed in nonprostatic tissues like brain, kidney, liver, lung, muscle, placenta, salivary gland, spleen, thyroid, and thymus. TM-PAP is also expressed in fibroblast, Schwann, and LNCaP cells, but not in PC-3 cells. In well-differentiated human prostate cancer tissue specimens, the expression of secretory PAP, but not TM-PAP, is significantly decreased. TM-PAP is localized in the plasma membrane-endosomal-lysosomal pathway and is colocalized with the lipid raft marker flotillin-1. No cytosolic PAP is detected. We conclude that the wide expression of TM-PAP in, for instance, neuronal and muscle tissues must be taken into account in the design of PAP-based immunotherapy approaches. [Cancer Res 2007;67(14):6549–54]
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