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At least 19 recordsLinked to original sources
PubMed1993

Comparison of prostate secretory protein with prostate specific antigen and prostatic acid phosphatase as a serum biomarker for diagnosis and monitoring patients with prostate carcinoma.

Serum prostate secretory protein (PSP) levels were measured in 49 patients with benign prostatic hyperplasia (BPH), 144 patients with various stages of prostatic carcinoma (CaP), and 82 CaP patients who were followed serially. PSP values were compared with serum levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). In the BPH group, PSP was elevated (> 10 ng/ml) in 41% of patients, whereas PSA (> 4 ng/ml) and PAP (> 3.3 ng/ml) were elevated in 39% and 23% of the cases, respectively. PSP levels were elevated in 48% of the CaP pretreatment specimens, compared to 79% for PSA and 40% for PAP. PSP levels in cancer patients who had intracapsular disease were about two to three times higher than those observed for PAP. PSP was found to be the only marker elevated in eight (6%) pretreatment CaP patient serum specimens, while PAP was never found to be elevated when PSA was normal. PSP serum concentrations correlated with the clinical course of the disease in 79% of patients, compared with 90% for PSA and 66% for PAP. In certain patients, monitored over time, disease correlation was reflected in serum values with only a single biomarker, i.e., 1% with PAP, 8% with PSP, and 10% with PSA. This study has shown that PSP is a less sensitive serum biomarker than PSA, but more sensitive than PAP for detection and monitoring the early stages of prostate cancer. This suggests that PSP as a biomarker may be a useful adjunct for the management of a subpopulation of low-stage and -grade CaP.

Acid Phosphatase↗
PubMed1997

Molecular cloning and gene expression analysis of PSP94 (prostate secretory protein of 94 amino acids) in primates.

Prostate secretory protein of 94 amino acids (PSP94) has shown the potential to be a diagnostic biomarker and a therapeutic agent for prostate cancer. Primates have been the main animal models for studying the biology of this molecule. We have cloned and analyzed the cDNA and promoter region of PSP94 from baboon (Papio anubis). Sequence divergence among baboon, monkey, pig, and human, in both the exons and 5'-flanking region indicates rapid evolution of the PSP94 gene. There are conserved steroid hormone response elements (SHRE) in the promoter region of all three primate species. Multiple, alternative transcripts starting near these SHREs and upstream to the TATA box were identified by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of 5'-cDNA ends (5' RACE) in primate prostatic tissues. This differential transcription initiation may be linked to androgen regulation of PSP94 gene expression. PSP94 transcripts were detected by RT-PCR in a wide variety of mucus-secreting tissues. However, the alternative transcripts were found only in the prostate. The distribution of the PSP94 protein in baboon secretory tissues was also examined by Western blot analysis using a polyclonal antibody against the human homolog. A positive immunoreactive band was detected, but it was weak, due probably to epitope divergence between the two species. In all young, healthy primate animals tested, the level of immunoreactive PSP94 in prostate tissues was lower than expected. In addition, RT-PCR combined with Southern blot analysis on prostate tissues in these animals failed to detect the PSP57 mRNA produced by alternative splicing of PSP94 primary transcript. These observations can be explained by the sexual immaturity and incomplete prostate development in these young primates. This explanation was supported by histological examination of their prostate during PSP94 immunohistochemistry.

Amino Acid Sequence↗
PubMed1993

Decreased expression of prostatic secretory protein PSP94 in prostate cancer.

cDNA libraries were generated from the prostate gland tissue obtained from a normal donor and from a patient with prostate cancer. Subtractive cDNA cloning was used to identify phenotype-specific cDNA sequences from both normal and cancerous prostate tissue. One clone, pN44, isolated from normal prostate tissue, codes for the prostate protein PSP94, expression of which appeared to be down-regulated in the cancerous cells. Rabbit antisera against PSP94 were generated, and these antisera can be used to detect PSP94 in urine. Two other clones, pN23a and pN141f, were also found to be down-regulated.

Amino Acid Sequence↗
PubMed1990

Generation and characterization of monoclonal antibodies to prostate secretory protein.

Monoclonal antibodies (MAbs) were produced against a highly purified preparation of prostate secretory protein (PSP) isolated from normal seminal plasma. Fifteen antibodies were selected for further evaluation based on their strong reactivity and specificity for PSP. All the MAbs had a specificity for prostate epithelial cells and none reacted to any of a variety of normal tissues as determined by immunoperoxidase staining. Six of the MAbs were selected for further immunohistochemical evaluation based on their ability to recognize different antigenic determinants. Using competitive binding immunoassays, a variety of overlapping specificities were observed with at least 2 distinct epitopes identified. Although some staining variability was noted, the 6 antibodies, in general, gave the same pattern of tissue reactivity. Both the normal prostate and the benign prostate hyperplastic ductal epithelial cells stained intensely, with 78 to 100% and 50-100% of the cells staining, respectively. The number and often the staining intensity of the tumor cells decreased as the tumor became more undifferentiated. Approximately 40 to 100% and 15 to 70% of the tumor cells stained in the moderately-differentiated and well-differentiated carcinoma tissues, respectively, whereas either no staining was observed or less than 20% of the tumor cells stained in the poorly-differentiated and undifferentiated tumors. Most of the metastatic prostate tumors showed either no staining or scattered staining in a few cells (i.e., less than 20%).

Adenocarcinoma↗
PubMedDate not supplied

Localization of the human prostatic secretory protein PSP94 and its mRNA in the epithelial cells of the prostate.

The histologic distribution of a prostatic secretory protein of 94 amino acids (PSP94) and its mRNA were examined simultaneously by conventional immunohistochemistry and in situ hybridization histochemistry. The results show localization of immunoreactive PSP94 and its mRNA in the epithelial cells of the prostate gland, thus providing strong evidence of PSP94 synthesis in these cells. Preliminary analysis of PSP94 by radioimmunoassay and of its mRNA by Northern blot analysis indicates that PSP94 biosynthesis in pathologic prostatic tissues is variable. The value of PSP94 as a marker of prostate gland secretory activity is discussed.

Carrier Proteins↗
PubMed1993

The potential use of prostatic secretory protein of 94 amino acid residues (PSP94) as a serum marker for prostatic tumor.

The serum concentrations of prostatic secretory protein of 94 amino acid residues (PSP94) as well as those of prostate-specific antigen (PSA) were determined in 40 patients with established prostatic carcinoma, prior to transurethral resection of the prostate. In a comparison with a control group of healthy men (n = 40) and a group of patients with histologically established benign prostatic hyperplasia (n = 40) no significant differences in PSP94 serum concentrations between the groups were observed. Similarly, correlations of PSP94 serum concentrations with prostatic carcinoma stages or grades were not detected. In contrast, and as expected, PSA behaved as a prostate tumor marker of known sensitivity and specificity. A correlation of PSP94 and PSA concentrations in sera of patients with benign prostatic hyperplasia and/or prostatic carcinoma could not be verified. PSP94 apparently does not fulfill the criteria of a serum marker for monitoring adenomas and/or carcinomas of the prostate.

Adult↗
PubMed1987

Excretion of three major prostatic secretory proteins in the urine of normal men and patients with benign prostatic hypertrophy or prostate cancer.

We have studied the mode of excretion of three prostatic secretory proteins, namely acid phosphatase (PAP), prostate-specific antigen (PSA) and beta-inhibin, in the urine of normal adult men, and we have determined the urinary levels of these proteins in men with benign prostatic hypertrophy (BPH) or adenocarcinoma. The output of the three proteins was highly variable during the day. In order to minimize these variations, 24-hour urine samples were collected thereafter. Our study showed that PAP concentrations in 50% of men with or without symptomatic BPH were similar to those of normal young men. In the remaining 50%, PAP was undetectable. In contrast, average PSA and beta-inhibin concentrations were higher in patients with BPH than in young men (p less than 0.05). The three markers were decreased or nondetectable in about half of the patients with untreated prostatic cancer. This phenomenon was even more pronounced in patients receiving hormonal treatment (castration or diethylstilbestrol). However, some of these patients still excreted normal amounts of PAP, PSA, and beta-inhibin. Urinary and serum PAP levels showed no correlation. These results indicate that urinary prostatic markers provide an easy means to study the behavior of the primary prostatic tumor. This information may be of potential value since it is not obtained with serum markers which originate mostly from metastatic cells.

Acid Phosphatase↗
PubMed1995

Expression of prostatic secretory protein (PSP)-like protein in porcine corpus luteum: isolation and characterization of a new gene encoding PSP94-like protein.

cDNA clones encoding stage-and/or space-specific genes in porcine ovarian follicles have been investigated by differential screening of cDNA libraries of granulosa cells and corpus luteum. A clone corresponding to mRNA preferentially expressed in the functional stage of corpus luteum was found to encode a protein similar to the human prostatic secretory protein, PSP94, which had been originally identified in male genital organs. The expression was detected widely in the functional corpora lutea by in situ hybridization histochemistry, but the signal was most prominent in the luteal cells surrounding blood vessels. In contrast, despite the structural similarity in their products, the expression of this newly identified gene was not detected in porcine prostate, suggesting that these structurally related proteins play different roles in mammalian genital organs.

Amino Acid Sequence↗
PubMed1992

Two-site monoclonal antibody-based immunoradiometric assay for measuring prostate secretory protein in serum.

We developed a double-determinant immunoradiometric assay for measuring serum prostate secretory protein (PSP), using monoclonal antibodies (MAb) against two different epitopes: MAb PSP-19 was the capture antibody and MAb PSP-6 was the tracer antibody. Assay sensitivity was 0.1 microgram/L. Analytical recovery of PSP was 93.5-104.6%, whereas the intra- and interassay mean CVs were 4.2% and 6.9%, respectively. In 92 normal men, ages greater than 50 years, the mean PSP concentration was 5.7 micrograms/L, with 10 (10.9%) men having concentrations greater than 10 micrograms/L. In contrast, 20 of 49 (40.8%) patients with benign prostate hyperplasia (BPH; mean PSP concentration 9.4 micrograms/L) and 46 of 100 (46%) patients with prostate cancer (mean PSP concentration 22.2 micrograms/L) had PSP concentrations greater than 10 micrograms/L. Mean serum PSP concentrations of the BPH (P less than 0.05) and prostate cancer (P less than 0.01) groups were significantly different from those of age-matched normal men. In a small group of patients, serial PSP concentrations correlated with the clinical course during therapy. Thus, PSP may be a useful marker for evaluating patients with prostate cancer.

Antibodies, Monoclonal↗
PubMed1987

Immunohistochemical localization of a prostatic secretory protein of 94 amino acids in normal prostatic tissue, in primary prostatic tumors and in their metastases.

Using the immunoperoxidase technique, we have studied in normal, hyperplastic and adenocarcinomatous prostates the tissue localization of an abundant 94 amino acid protein secreted by prostatic epithelial cells. In normal and hyperplastic prostates, strong immunoreactivity was found exclusively in glandular epithelial cells. No reaction was observed over the stroma. In well differentiated adenocarcinoma, the acinar cells were generally stained less intensely than in benign prostatic hyperplasia while in poorly differentiated tissue, strongly positive immunoperoxidase staining was found in some cancer cells scattered in the stroma. All prostatic cancer tissues examined (N = 21), with the exception of one, exhibited at least a few positive immunoreactive areas for the 94 amino acid secretory protein. In addition, immunoperoxidase staining was observed in lung and bone marrow metastases respectively in two patients with prostatic carcinoma. All other normal tissues and non-prostatic cancers studied to date were negative. These results suggest that this new marker could be a useful addition to prostatic acid phosphatase and prostate specific antigen.

Adenocarcinoma↗
PubMed1996

A new scalable purification procedure for prostatic secretory protein (PSP94) from human seminal plasma.

A simple three-step procedure for the purification of native prostate secretory protein (PSP94) from human seminal plasma is described. The steps are ammonium sulfate fractionation followed by a Macro-Prep S support (cation) flowthrough process and the final Macro-Prep high Q support (anion exchange) chromatography using two step-gradient elution. The benefits of this procedure lie in its simplicity, speed, and relatively inexpensive materials, thus providing advantages over the previously reported schemes. The purity of the product as judged by single band on SDS-polyacrylaminde gel electrophoresis was equivalent to that attained by analytical HPLC anion exchange procedure. Yields were in the range of 18-25 mg highly pure PSP94 per 50 ml of seminal plasma. The desalted, lyophilized, purified PSP94 sample was characterized by SDS-PAGE, Western blot, and N-terminal sequencing. All parameters tested confirm its identity. Preliminary data show that this procedure is suitable for a large-scale production. The direct quantitation of PSP94 by SDS-PAGE and densitometric image analysis at various purification steps for evaluating the recovery of PSP94 is described. The results obtained show that this is an efficient strategy for preparation of highly purified native PSP94.

Blotting, Western↗
PubMed1990

Characterization of a monoclonal antibody specific for prostatic secretory protein of 94 amino acids (PSP94) and development of a two-site binding enzyme immunoassay for PSP94.

Purified prostatic secretory protein of 94 amino acids (PSP94) was used to generate polyclonal rabbit anti-PSP94 IgG and a murine monoclonal antibody 6B6 (mAB6B6). Both antibodies were highly specific for PSP94 by immunoblotting. Immunohistochemical studies demonstrated the specificity of mAB6B6 for human prostatic epithelial tissue. A two-site binding enzyme immunoassay for the detection of PSP94 was developed using a combination of the antibodies. The sandwich-ELISA yielded satisfactory results when mAB6B6 complexed to peroxidase conjugated goat anti-mouse-IgG (Fc) was incubated simultaneously with the sample. The assay has a dynamic range of 2-30 micrograms/l. This immunoassay was employed to measure PSP94 in male human sera (8 +/- 4 micrograms/l), female human sera (5.7 +/- 3.4 micrograms/l), follicular fluid (3.9 +/- 2.9 micrograms/l) and human seminal plasma (1.02 +/- 0.8 g/l).

Adolescent↗
PubMed1991

Prostatic secretory protein PSP94: gene organization and promoter sequence in rhesus monkey and human.

As part of an effort to determine the molecular basis of the prostate-specificity of PSP94, a prostatic secretory protein of 94 amino acids, we have characterized its gene in Rhesus monkey and in human. In both species, the 18 kb gene is organized in four exons and three introns. The sequence of the 0.8 kb promoter region is highly homologous (93.8%) between the two species. A conserved steroid-hormone responsive element was identified in this region, and an estrogen-responsive element in the first intron, suggesting possible regulation of this gene by sex hormones.

Amino Acid Sequence↗
PubMed1995

Alternative splicing of PSP94 (prostatic secretory protein of 94 amino acids) mRNA in prostate tissue.

While performing reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of total mRNA from prostate cancer specimens, two forms of PSP94 cDNA were detected. RT-PCR products were analysed by Southern blotting and probing with exon-specific oligonucleotides. In the short form of PSP94 mRNA, designated as PSP57, exon III was found to be deleted. The two mRNA forms were confirmed by cloning and sequencing of the RT-PCR products and were found to result from alternative splicing. The alternatively spliced form, PSP57, was characterized by sequence analysis. PSP94 and PSP57 possess identical exons I and II, including identical secretion signal peptide and the 5' untranslated sequences. PSP57 has a frame-shifted exon IV and encodes a putative 57 amino acid protein with a novel, highly basic C-terminus of 41 amino acids. PSP57 mRNA was detected in other urogenital tissues (kidney, bladder) and in most tumor cell lines tested, but was not detectable in other tissues such as breast and lung. In prostate tumor cell lines, PSP57 mRNA was aberrantly spliced and localized in the nuclear fraction of the cell. Our results suggest the possible existence of a novel PSP protein that originates from alternative splicing of PSP94 mRNA in urogenital tissues.

Aged↗
PubMed1988

Correct processing and secretion of a human prostatic secretory protein (PSP94) in Escherichia coli.

The cDNA for PSP94, a cysteine-rich protein secreted by the human prostate, was unidirectionally digested with exonuclease III to generate deletion mutants with varying 5' ends. These were placed under the control of the lac promoter of the Bluescribe plasmid (pbs) to encode hybrid proteins containing the N terminus of beta-galactosidase (beta Gal) and various fragments of PSP94. Escherichia coli clones transformed by these constructs and expressing PSP94 epitopes were identified by radioimmunoassay of cellular and periplasmic extracts. One such clone (I-25) secreted most of its immunoreactive material into the periplasmic space. Nucleotide sequencing showed that a new consensus ribosome-binding site had been generated fortuitously, allowing expression of pre-PSP94 free of any beta Gal sequence. Periplasmic PSP94 is indistinguishable from the natural human protein, indicating correct processing and folding of this cysteine-rich protein in bacteria.

Amino Acid Sequence↗
PubMed1997

Analysis of epitope structure of PSP94 (prostate secretory protein of 94 amino acids): (II). Epitope mapping by monoclonal antibodies.

PSP94 has shown potential to be a serum biomarker for evaluating prostate cancer. Studies of the epitope structure is crucial for this endeavour. In this article, we have used 15 different monoclonal antibodies (MAb) to analyse the epitope structure of PSP94 and to compare with the results obtained from our previous work using polyclonal antibody and recombinant PSP94. Firstly, we determined the relative activities of the 15 MAb population by direct and competitive ELISA. The two predominant MAbs (MAb PSP-6 and -19) in 15 MAbs were selected for further studies of the epitope structure. By comparing the binding activities of recombinant GST-PSP94 and natural PSP94 with MAbs, and by comparing their affinity with MAbs in an in vitro denaturing experiment, PSP94 was shown to have a similar, prevalently linear epitope structure as we demonstrated by polyclonal antibody. Using recombinant GST fusion protein with PSP94 and with each half of the N- and C-terminal 47 amino acids (GST-PSP-N47/C47) in E. coli cells, the different epitopes recognized by 15 monoclonal antibodies were delineated and the polar distribution of the epitope structure of PSP94 was characterized. Results of direct ELISA of recombinant N47 and C47 and their competitive binding against natural PSP94 (competitive ELISA) showed that the N- and C-termini represent the immuno-dominant and immuno-recessive area separately. A majority of the monoclonal antibodies (12/15) showed preferential binding of the N-terminal sequence of the PSP94 protein. Using GST-PSP-N47 as a standard protein, an epitope map of the 15 monoclonal antibodies was obtained. The results of this study will help to define the clinical utility of PSP94.

Animals↗
PubMed1996

Recombinant PSP94 (prostate secretory protein of 94 amino acids) demonstrates similar linear epitope structure as natural PSP94 protein.

PSP94 has the potential to be a useful diagnostic marker and therapeutic agent in prostate cancer. Recently, different immunoassay systems for quantitative analysis of PSP94 in clinical samples have been developed, but the epitope structure of PSP94 protein has not been elucidated. In this study, we report an Escherichia coli expression system for recombinant GST-PSP94 fusion protein. GST-PSP94 contains antigenic determinants similar to natural PSP94 protein (determined both by Western blotting experiments and by ELISA) and can be used to study the structure of natural PSP94 antigen. Since GST-PSP94 was expressed in E. coli and purification involved a denaturing process, we propose that the epitope structure of PSP94 is linear and largely dependent on the primary amino acid sequence, rather than conformational structure. This hypothesis was supported by reciprocal competition in ELISA among natural, GST-PSP94 fusion protein, and purified recombinant PSP94 protein. The results demonstrate that the various forms of PSP94 can compete with each other in binding to rabbit PSP94 polyclonal antibody, although the natural PSP94 has a slightly higher affinity. When natural and recombinant PSP94 protein were denatured in vitro with urea and alkali, no effect on the binding to antibody was found. The epitope activity of natural PSP94 was also shown to be resistant to the treatment of detergent and reducing agent. The location of one of the linear epitopes recognized by the PSP94 antibody was determined to be in the N-terminus by using two synthetic peptides representing N- and C-terminal sequences. Competitive ELISA between the N-terminal peptide and PSP94 protein indicate that both natural and GST-PSP94 have similar immunoactive N-termini.

Animals↗