Abstract
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.
Highlights
Prostate cancer is the most common cancer in men and the second leading cause of cancer death in the Western countries
To obtain cDNA encoding rat TM-prostatic acid phosphatase (PAP), total RNA isolated from rat prostate was amplified by reverse transcription-PCR (RT-PCR) using primers 5¶-ACCATGAGAGCTGTCCCTCTG-3¶ and 5¶-TCAGATGTTCCGATACAC-3¶ designed from the rat genomic region, which we found in silico based on our hypothesis of high similarity in rat and mouse PAP gene structure and the peptide sequence of a possible TM domain
Comparison of the exon-intron junction suggests that rat, mouse, and human PAP variants are derived by alternative splicing
Summary
Prostate cancer is the most common cancer in men and the second leading cause of cancer death in the Western countries. Our results show that PAP has two splicing variants encoding a secretory form and a type I transmembrane (TM) protein, which is in vesicles and membranes and is widely expressed in many nonprostatic cells and tissues. Total RNA was isolated from human and mouse tissue specimens, mouse fibroblasts, SW-10, LNCaP, and PC-3 cells, and used as a template.
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