Prostatic acid phosphatase is not a prostate specific target.
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 NH(2)-terminal phosphatase activity and the COOH-terminal lysosomal targeting signal (YxxPhi). 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.
Quintero
Ileana B
IB
Research Center for Molecular Endocrinology and WHO Collaborating Centre, Biocenter Oulu, University of Oulu, Finland.
Araujo
César L
CL
Pulkka
Anitta E
AE
Wirkkala
Riikka S
RS
Herrala
Annakaisa M
AM
Eskelinen
Eeva-Liisa
EL
Jokitalo
Eija
E
Hellström
Pekka A
PA
Tuominen
Hannu J
HJ
Hirvikoski
Pasi P
PP
Vihko
Pirkko T
PT
D000135:Acid Phosphatase; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D011467:Prostate / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D008565:Membrane Proteins; C106354:flotillins; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases