• Biomolecules & Therapeutics
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• v.21 no.1
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• pp.10-20
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• 2013

Prostate cancer is one of the most prevalent non-skin related cancers. It is the second leading cause of cancer deaths among males in most Western countries. If prostate cancer is diagnosed in its early stages, there is a higher probability that it will be completely cured. Prostatic acid phosphatase (PAP) is a non-specific phosphomonoesterase synthesized in prostate epithelial cells and its level proportionally increases with prostate cancer progression. PAP was the biochemical diagnostic mainstay for prostate cancer until the introduction of prostate-specific antigen (PSA) which improved the detection of early-stage prostate cancer and largely displaced PAP. Recently, however, there is a renewed interest in PAP because of its usefulness in prognosticating intermediate to high-risk prostate cancers and its success in the immunotherapy of prostate cancer. Although PAP is believed to be a key regulator of prostate cell growth, its exact role in normal prostate as well as detailed molecular mechanism of PAP regulation is still unclear. Here, many different aspects of PAP in prostate cancer are revisited and its emerging roles in other environment are discussed.

• Journal of Life Science
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• v.21 no.6
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• pp.893-900
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• 2011

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-${\kappa}B$, TNF-${\alpha}$, 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.

• BMB Reports
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• v.29 no.5
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• pp.417-422
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• 1996

In clonal sublines with different metastatic ability derived from Dunning rat prostate tumor, phosphoamino acid levels of cellular proteins were determined. Cell lines with high metastatic ability exhibited 5-fold higher phosphotyrosine level than did cell lines with low metastatic ability, while the contents of phosphoserine and phosphothreonine were similar among cell lines examined, All cell lines showed similar activities of protein tyrosine kinases as well as overall protein kinases. Phosphotyrosine protein phosphatase (PTPP) activities of the cells with high metastatic ability were very low, compared to those of the cells with low metastatic ability, suggesting that the different phosphotyrosine levels among the cell lines were due to the difference in PTPP activities rather than protein tyrosine kinase activities. Cellular activities of prostatic acid phosphatase (PAcP), which has been reported to possess phosphotyrosine protein phosphatase activity, were shown to be inversely related to the phosphotyrosine levels and metastatic abilities of the prostate tumor cells, These results suggest that cellular PAcP activity, regulating phosphotyrosine levels of cellular proteins, is closely connected with the metastatic process in prostate tumor cells and can be utilized as a good biochemical marker for the diagnosis of metastasis of prostate tumor.

• Molecules and Cells
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• v.38 no.2
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• pp.171-179
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• 2015

Prostatic acid phosphatase (PAP) expression increases proportionally with prostate cancer progression, making it useful in prognosticating intermediate to high-risk prostate cancers. A novel ligand that can specifically bind to PAP would be very helpful for guiding prostate cancer therapy. RNA aptamers bind to target molecules with high specificity and have key advantages such as low immunogenicity and easy synthesis. Here, human PAP-specific aptamers were screened from a 2'-fluoropyrimidine (FY)-modified RNA library by SELEX. The candidate aptamer families were identified within six rounds followed by analysis of their sequences and PAP-specific binding. A gel shift assay was used to identify PAP binding aptamers and the 6N aptamer specifically bound to PAP with a Kd value of 118 nM. RT-PCR and fluorescence labeling analyses revealed that the 6N aptamer bound to PAP-positive mammalian cells, such as PC-3 and LNCaP. IMR-90 negative control cells did not bind the 6N aptamer. Systematic minimization analyses revealed that 50 nucleotide sequences and their two hairpin structures in the 6N 2'-FY RNA aptamer were equally important for PAP binding. Renewed interest in PAP combined with the versatility of RNA aptamers, including conjugation of anti-cancer drugs and nano-imaging probes, could open up a new route for early theragnosis of prostate cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2149-2152
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• 2012

Objective: This study was performed to assess prostate biomarkers with reference to body mass index and duration of prostate cancer. Materials and Methods: A hospital based retrospective study was undertaken using data retrieved from the register maintained in the Department of Biochemistry of Manipal Teaching Hospital, Pokhara, Nepal between $1^{st}$ January, 2009 and $28^{th}$ February, 2012. Biomarkers studied were prostate specific antigen (PSA), acid phosphatase (ACP) and prostatic acid phosphatase (PAP), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (${\gamma}GT$). Demographic data including age, duration of disease, body weight, height and body mass index (BMI) were also collected. Duration of disease was categorized into three groups: <1 year, 1-2years and >2 years. Similarly, BMI ($kg/m^2$) was categorized into three groups: <23 $kg/m^2$, 23-25 $kg/m^2$ and >25 $kg/m^2$. Descriptive statistics and testing of hypothesis were used for the analysis using EPI INFO and SPSS 16 software. Results: Out of 57 prostate cancers, serum level of PSA, ACP and PAP were increased above the cut-off point in 50 (87.5%), 30 (52.63%) and 40 (70.18%) respectively. Serum levels of PSA, ACP and PAP significantly declined with the duration of disease after diagnosis. We observed significant and inverse relation between PSA and BMI. Similar non-signficiant tendencies were apparent for ACP and PAP. Conclusions: Decreasing levels of prostate biomarkers were found with the duration of prostate cancer and with increased BMI. Out of prostate biomarkers, PSA was found to be significantly decreased with the duration of disease and BMI.

• BMB Reports
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• v.56 no.7
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• pp.392-397
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• 2023

In this study, recombinant Fc-fused Prostate acid phosphatase (PAP) proteins were produced in transgenic plants. PAP was fused to immunoglobulin (Ig) A and M Fc domain (PAP-IgA Fc and PAP-IgM Fc), which were tagged to the ER retention sequence KDEL to generate PAP-IgA FcK and PAP-IgM FcK. Agrobacterium-mediated transformation was performed to produce transgenic tobacco plants expressing four recombinant proteins. Genomic PCR and RT-PCR analyses confirmed the transgene insertion and mRNA transcription of PAP-IgA Fc, PAP-IgM Fc, PAP-IgA FcK, and PAP-IgM FcK in tobacco plant leaves. Western blot confirmed the expression of PAP-IgA Fc, PAP-IgM Fc, PAP-IgA FcK, and PAP-IgM FcK proteins. SEC-HPLC and Bio-TEM analyses were performed to confirm the size and shape of the plant-derived recombinant PAP-Fc fusion proteins. In mice experiments, the plant-derived IgA and IgM Fc fused proteins induced production of total IgGs including IgG1 against PAP. This result suggests that IgA and IgM Fc fusion can be applied to produce recombinant PAP proteins as a prostate cancer vaccine in plant expression system.

• Advances in Traditional Medicine
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• v.7 no.3
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• pp.304-310
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• 2007

Monocrotophos was administered orally to adult male albino mice at dose level of 3.0 mg/kg body weight/day/mice for 50 days. The treatment has found to affect spermatogenesis as well as the endocrine functions of the testis as indicated by gravimetric, histopathological and biochemical changes. The treatment has caused degenerative changes in the seminiferous tubules and Leydig cells of the testis and regression of the epididymis, seminal vesicle, vas deferens, prostate, Cowper's gland and levator ani. Similarly, cauda epididymal sperm count and sperm motility have shown significant reduction. There was a significant reduction in the protein, glycogen, sialic acid, acid and alkaline phosphatase and increase in cholesterol in the testis of monocrotophos treated mice compared with the control. The causative factors for these changes due to monocrotophos administration were discussed.

• Advances in Traditional Medicine
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• v.3 no.3
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• pp.133-140
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• 2003

Petroleum ether, chloroform and ethanol extracts of the seeds of Melia azedarach Linn. administered orally to male rats at the dose level of 25 mg/100 g body weight for 48 days showed antispermatogenic activity, as the number of spermatocytes, spermatids and spermatozoa was decreased. The total cholesterol content was increased while protein and glycogen contents were decreased. The acid phosphatase content was also decreased while that of alkaline phosphatase increased. At the same time the weight of caput and cauda epididymis, prostate gland, seminal vesicle and Levator Ani muscle was decreased indicating its antiandrogenic property. Of the three extracts, the petroleum ether extract was more potent in its antispermatogenic and antiandrogenic activities and did not produce any sings of toxicity upto a dose of 25 mg/100 g body weight oral administration. After subjecting it to preliminary phytochemical screening the petroleum ether extract showed positive tests for steroids and saponins.

• KSBB Journal
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• v.24 no.1
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• pp.80-88
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• 2009

Human prostatic acid phosphatase (PAP), with comprehensive homology to glandular kallikrein, are representative serum biomarkers of prostate cancer. Dendritic cell (DC), which is the potent antigen-presenting cells(APC) in the immune system, can induce strong T cell responses against viruses, microbial pathogens, and tumors. Therefore, the immunization using DC loaded with tumor-associated antigens is a powerful method for inducing anti-tumor immunity. The CTP (Cytoplasmic Transduction Peptide) technology developed by Creagene which can transport attached bio-polymers like nucleic acids or proteins into the cell with high permeation efficiency. As the active forms of PAP can mediate apoptotic processing, we used multimer forms of PAP as an inactive form for antigen pulsing of DCs. In this study, multimeric forms of CTP-rhPAP was obtained according to the advanced purification process and subsequently confirmed by gel filtration chromatography, western blot and Dynamic Light Scattering. Therefore, CTP-conjugated PA multimers transduced into the cytoplasm were efficiently presented on the cell surface without any harm effect on cells via MHC class I molecules and result in induction of a large number of effector cell.

• The Korean Journal of Pharmacology
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• v.10 no.2
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• pp.39-42
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• 1974

Despite a considerable amount of investigation there continues to be disagreement concerning the proteins present in human seminal plasma. Recently their identification has assumed a greater importance following evidence that infertility in men and women may have an immunological cause (Katsh, 1959; Quinlivan, 1969). Seminal plasma is composed of fluids secreted by the prostate, seminal vesicles, ampullae, ducti deferentes, bulbourethral (Cowper's) glands, urethral(Littre's) glands and the epididymes. Prostatic juice, one of the major components of seminal plasma, has an important role in secretion of acid phosphatase and prostaglandin. A few studies have been reported of human prostatic juice, since, in human subjects, there were some problems in studying prostatic juice due to quite small amount of secretion and possibility of contamination with fluids from the seminal vesicles and ejaculatory ducts. The purpose of the present study was to determine the basic components of proteins in human prostatic juice. Prostatic juice was obtained from normal healthy man of $20{\sim}30\;year-old$ by massage of the prostate, and protein components were separated by means of disc electrophoresis. The results are summarized as follows; 1) Total numbers of protein fractions of normal human serum and prostatic juice are $14{\sim}18$ bands and $9{\sim}12$ bands, respectively. Prostatic juice produces two deeply staining bands which appear similar to those formed by $beta-_1$ globulin and albumin. 2) $Alpha-_1$ globulin area in the fractions of prostatic juice shows 4 bands and one more band is found than that of serum. On the other hand, the fractions of immunoglobulin and $alpha-_2$ globulin areas are eight in serum and it has three bands more than that of prostatic juice. 3) $Alpha-_1$ globulin area in the prostatic juice is more deeply stained than that of serum. In contrast with $alpha-_1$ globulin area, immunoglobulin and $alpha-_2$ globulin areas in the prostatic juice show weaker staining than serum.