Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q04609 (prostate-specific membrane antigen)
 1,287 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A better understanding of the molecular changes associated with the onset and progression of prostate cancer may provide us with a rational basis for the development of new diagnostic and therapeutic tools. Likewise, the recent identification of critical biochemical pathways, including angiogenesis, programmed cell death, cell adhesion and signal transduction, provide us with promising targets for therapeutic approaches. Furthermore, the identification and characterization of new tumor-specific antigens or prostate-cancer-specific gene promoters could be instrumental for the development of new treatment modalities. Many research groups are trying to identify genes that are involved in prostate cancer development and which may serve as new tumor markers and potential targets for therapy. In addition to prostate-specific antigen, prostate-specific membrane antigen and human kallikrein-2, the recently identified prostate stem cell antigen may also provide us with a new tool for the diagnosis and treatment of prostate cancer. Our own studies led to the identification of DD3, a gene that is strongly overexpressed in human prostatic cancers and the expression of which appears to be restricted to the prostate. Further studies are necessary to establish the clinical usefulness of these new prostate-cancer-specific genes for the management of prostate cancer patients.
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PMID:Changes in gene expression and targets for therapy. 1032 97

Prostatic small cell carcinoma is an aggressive subtype of prostate cancer that usually appears as a progression of the original adenocarcinoma. We describe here the WISH-PC2, a novel neuroendocrine xenograft of small cell carcinoma of the prostate. This xenograft was established from a poorly differentiated prostate adenocarcinoma and is serially transplanted in immune-compromised mice where it grows within the prostate, liver, and bone, inducing osteolytic lesions with foci of osteoblastic activity. It secretes to the mouse Chromogranin A and expresses prostate plasma carcinoma tumor antigen-1, six-transmembrane epithelial antigen of the prostate, and members of the Erb-B receptor family. It does not express prostate-specific antigen, prostate stem cell antigen, prostate-specific membrane antigen, and androgen receptor, and it grows independently of androgen. Altogether, WISH-PC2 provides an unlimited source in which to study the involvement of neuroendocrine cells in the progression of prostatic adenocarcinoma and can serve as a novel model for the testing of new therapeutic strategies for prostatic small cell carcinoma.
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PMID:WISH-PC2: a unique xenograft model of human prostatic small cell carcinoma. 1111 33

To identify genes that are differentially up-regulated in prostate cancer of transgenic adenocarcinoma mouse prostate (TRAMP) mice, we subtracted cDNA isolated from mouse kidney and spleen from cDNA isolated from TRAMP-C1 cells, a prostate tumor cell line derived from a TRAMP mouse. Using this strategy, cDNA clones that were homologous to human six-transmembrane epithelial antigen of the prostate (STEAP) and prostate stem cell antigen (PSCA) were isolated. Mouse STEAP (mSteap) is 80% homologous to human STEAP at both the nucleotide and amino acid levels and contains six potential membrane-spanning regions similar to human STEAP. Mouse PSCA (mPsca) shares 65% homology with human PSCA at the nucleotide and amino acid levels. mRNA expression of mSteap and mPsca is largely prostate-specific and highly detected in primary prostate tumors and metastases of TRAMP mice. Both mSteap and mPsca map to chromosome 5. Another known gene coding for mouse prostate-specific membrane antigen (mPsma) is also highly expressed in both primary and metastatic lesions of TRAMP mice. These results indicate that the TRAMP mouse model can be used to effectively identify genes homologous to human prostate-specific genes, thereby allowing for the investigation of their functional roles in prostate cancer. mSteap, mPsca, and mPsma constitute new tools for preventative and/or therapeutic vaccine construction and immune monitoring in the TRAMP mouse model that may provide insights into the treatment of human prostate cancer.
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PMID:Murine six-transmembrane epithelial antigen of the prostate, prostate stem cell antigen, and prostate-specific membrane antigen: prostate-specific cell-surface antigens highly expressed in prostate cancer of transgenic adenocarcinoma mouse prostate mice. 1147 26

Carcinoma of the prostate is the second leading cause of male cancer-related death in the United States. Better indicators of prostate cancer presence and progression are needed to avoid unnecessary treatment, predict disease course, and develop more effective therapy. Numerous molecular markers have been described in human serum, urine, seminal fluid, and histological specimens that exhibit varying capacities to detect prostate cancer and predict disease course. However, to date, few of these markers have been adequately validated for clinical use. The purpose of this review is to examine the current status of these markers in prostate cancer and to assess the diagnostic potential for future markers from identified genes and molecules that display loss, mutation, or alteration in expression between tumor and normal prostate tissues. In this review we cite 91 molecular markers that display some level of correlation with prostate cancer presence, disease progression, cancer recurrence, prediction of response to therapy, and/or disease-free survival. We suggest criteria to consider when selecting a marker for further development as a clinical tool and discuss five examples of markers (chromogranin A, glutathione S-transferase pi 1, prostate stem cell antigen, prostate-specific membrane antigen, and telomerase reverse transcriptase) that fulfill some of these criteria. Finally, we discuss how to conduct evaluations of candidate prostate cancer markers and some of the issues involved in the validation process.
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PMID:Detection of prostate cancer and predicting progression: current and future diagnostic markers. 1521 24

There has been a resurgence of interest in developing noncytotoxic immune therapies for patients with either hormone-naive biochemically relapsed post-primary therapy or castrate metastatic prostate cancer. The rationale for developing an immunotherapeutic approach has been based on the overexpression and underglycosylation of a wide variety of altered "self" molecules including prostate-specific antigen (PSA), acid phosphatase (ACP), prostate stem cell antigen (PSCA), and prostate-specific membrane antigen (PSMA), which can serve as targets for immune recognition and attack. In addition, such a strategy could theoretically make use of the patient's immune system to fight the tumor particularly if their disease is of reasonably low volume. A variety of immunotherapeutic approaches have been explored through phase I, II, and now phase III trials demonstrating that immunologic tolerance could be broken, as evidenced by the development of hightiter antibodies and T-cell responses specific for the tumor. What appears to be revolutionizing the immunotherapy field is the combination of vaccines with cytokines or immune modulators, which not only potentiate immune reactivity in vivo but foster dramatic antitumor responses. This review explores the challenges now faced in establishing a role for immune therapies for prostate cancer treatment.
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PMID:Emerging role of immunotherapy in the management of prostate cancer. 1744 37

Numerous efforts exist for developing primary prostate cancer cultures for studying the biology of this tumor entity and for evaluation of the effectiveness of novel therapies. However, there is doubt if cultures that represent the fully differentiated phenotype can be established. The aim of the present study was to characterize primary outgrowing prostate epithelial cells due to their basal or luminal characteristics and their potential for serving as androgen-responsible model. From fresh prostate cancer radical prostatectomy specimens, pieces of approximately 2-4 mm diameter were placed on top of transwell culture chambers, which were coated with matrigel and cultured in prostate epithelial selection medium with 10% fetal calf serum. The monolayer of outgrowing cells was incubated with a physiological concentration of 1 nM dihydrotestosterone (DHT). One group was additionally cultivated without DHT and another group was treated with the 5-alpha-reductase-inbitors MK-368 and MK-905. From the monolayer of the outgrowing cells, RNA was isolated and the expression of androgen receptor (AR), prostate-specific antigen (PSA), Kallikrein 2 (KlK2), prostate-specific membrane antigen (PSMA), and prostate stem cell antigen (PSCA), cytokeratin (CK)5, and CK18 was determined by realtime quantitative PCR. The outgrowing cells from the prostate cancer tissue pieces could be characterized as epithelial cells with basal and transit amplifying characteristics as shown by co-expression of CK5 and CK18. In all cultures, a very low expression of the luminal cell marker genes AR, PSA and KLK2 was measured. The levels of PSCA were clearly higher with a broad variation. Upon cultivation without DHT or treatment with alpha-reductase inhibitors no regulation of AR, PSA and KlK2 was found. Due to the co-expression of basal and luminal marker genes, primary prostate cancer cultures can be charaterized as models of transit amplifying cells of the prostatic epithelium. They do not represent the differentiated secretory androgen-responsive cell phenotype.
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PMID:Primary prostate cancer cultures are models for androgen-independent transit amplifying cells. 2004 8

Tumor markers (TMs) play an important role in clinical rapid screening and diagnosis for prostate cancer (PCa). In this study, we describe a competitive method to establish the multiplex suspension array by tumor biomarkers coated on distinguishable microbeads which competing with free biomarkers for their complementary antibodies (Ab) in one single reaction system for simultaneous and combined detection of prostate TMs in human serum. The volumes of the targets coupled onto the beads and their complementary Abs were optimized. The suspension array standard curves correlated well with PCa biomarkers (R(2)>0.9968). PCa biomarker levels were quantified using median fluorescent intensities. The working ranges of prostate-specific antigen (PSA), prostate stem cell antigen (PSCA), prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP) were 0.47-502.94, 1.00-923.35, 1.00-524.79, and 1.73-176.07ngmL(-1) in serum samples, respectively. This method was compared to indirect competitive enzyme linked immunosorbent assay. It was found that high concordance between the two technologies resulted from serum samples of the eight PCa patients. The multiplex suspension array technology is specific to PCa biomarkers, displayed no significant cross-reactivity, and remains stable for 6 months. We also characterized the bead surface microstructures under different conditions employing a field emission scanning electron microscope. The suspension array is a straightforward and reliable method for analysis of multiple TMs with simple operation, high sensitivity at a low cost.
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PMID:Simultaneous and combined detection of multiple tumor biomarkers for prostate cancer in human serum by suspension array technology. 2356 27