Roles of Prostatic Acid Phosphatase in Prostate Cancer

Abstract

Prostatic acid phosphatase (PAP) is one of the widely used biomarkers in the diagnosis of prostate cancer. It was initially identified in 1935 and is the most abundant phosphatase in the human prostate. PAP is a prostate-specific enzyme that is synthesized in prostate epithelial cells. It belongs to the acid phosphatase group that shows enzymatic activity in acidic conditions. PAP is abundant in prostatic fluid and is thought to have a role in fertilization and oligospermia. It also has a potential role in reducing chronic pain. But one of the most apparent functions of PAP is the dephosphorylation of macromolecules such as HER-2 and PI3P that are involved in the ERK1/2 and MAPK pathways, which in turn leads to inhibition of cell growth and tumorigenesis. Currently, clinical trials using PAP DNA vaccine are underway and FDA-approved immunotherapy using PAP is commercially available. Despite these clinically important aspects, molecular mechanisms underlying PAP regulation are not fully understood. The promoter region of PAP was reported to be regulated by NF-κB, TNF-α, IL-1, androgen and androgen receptors. Here, the features of PAP gene and protein structures together with the function, regulation and roles of PAP in prostate cancer are discussed.

Cancer-associated fibroblast-derived gene signatures predict radiotherapeutic survival in prostate cancer patients

“…ACPP (prostate acid phosphate) is a secreted glycoprotein enzyme that is produced by in epithelial cells of the prostate gland in humans. ACPP has been reported as a prognostic biochemical indicator for monitoring of prostate cancer progression [ 35 ]. ACPP is also shown to promote the osteoblastic reaction in CRPC bone metastases [ 36 ].…”

Emerging Roles of Human Prostatic Acid Phosphatase

“…Alternative splicing generates two types of PAP transcripts; transmembrane PAP which consists of 11 exons (exon 1-9, 10a and 11), and cellular and secretory PAPs having 10 exons (exon 1-9 and 10b) (Zelivianski et al ., 1998; Veeramani et al ., 2005; Kong et al ., 2011). The length of 3’-UTR of transmembrane PAP is shorter than those of cellular and secretory PAPs: 405 bp versus 874 bp (Kong et al ., 2011). The molecular mechanisms underlying PAP gene regulation are not fully understood.…”

“…When androgen levels are normal, the −151/−140 site is involved in enhancing PAP transcription level. However, when androgen level is low, the +218/+229 and +244/+255 sites act as negative regulators of PAP transcription (Porvari et al ., 1995; Kong et al ., 2011). These findings imply that the androgen is an essential factor for human PAP expression.…”

Loss of prostatic acid phosphatase and α-synuclein cause motor circuit degeneration without altering cerebellar patterning

“…The two types of PAP transcripts are generated by alternative splicing; transmembrane PAP (TMPAP) which consists of 11 exons (exon 1–9, 10a and 11), and cellular and secretory PAPs having 10 exons (exon 1–9 and 10b) [13–15]. TMPAP is a member of the plasma membrane-endosomal-lysosomal pathway and the length of the 3’ untranslated region of TMPAP is shorter than those of cellular and secretory PAPs: 405 bp versus 874 bp [15,16]. As an important marker for prostatic carcinoma, PAP was identified long before the introduction of prostate specific antigen (PSA) [14,17,18].…”