Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of FAS polymorphisms in prostate cancer has not been studied. Using the PCR-based restriction fragment-length polymorphism methodology, we evaluated FAS gene locus -670 genotypes in DNA from 904 men: 657 prostate cancer patients and 247 healthy controls. We found that carriers of AG or GG genotypes have a statistically significant protection (odds ratio (OR)=0.30; confidence interval (CI): 0.20-0.44 and OR=0.22; CI: 0.12-0.74, respectively) for disease with extra-capsular invasion. Taken together, a 72% protection was found for G allele carriers (OR=0.28; CI: 0.19-0.41). Fas exist as membrane-bound and soluble forms and with opposite roles. They derive from the same gene by alternative splicing. Membrane Fas receptors trigger apoptosis whereas, on the other hand, soluble Fas (sFas) bind to Fas ligand antagonizing Fas-Fas ligand apoptotic pathway. Our results suggest that G allele may reduce sFas levels preventing the apoptotic inhibition caused by the soluble form.
Prostate Cancer Prostatic Dis 2008
PMID:Association between FAS polymorphism and prostate cancer development. 1766 65

Prostate-specific membrane antigen (PSMA) is a membrane-bound cell surface peptidase which is over-expressed in prostate cancer cells. The enzymatic activities of PSMA are understood but the role of the enzyme in prostate cancer remains conjectural. We previously confirmed the existence of a hydrophobic binding site remote from the enzyme's catalytic center. To explore the specificity and accommodation of this binding site, we prepared a series of six glutamate-containing phosphoramidate derivatives of various hydroxysteroids (1a-1f). The inhibitory potencies of the individual compounds of the series were comparable to a simple phenylalkyl analog (8), and in all cases IC50 values were sub-micromolar. Molecular docking was used to develop a binding model for these inhibitors and to understand their relative inhibitory potencies against PSMA.
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PMID:Phosphoramidate derivatives of hydroxysteroids as inhibitors of prostate-specific membrane antigen. 1802 82

To study the differential expression of cell membrane-bound receptors and their potential role in growth and/or survival of the tumor cells, highly purified follicular lymphoma cells were analyzed, using gene expression analysis, and compared to non-malignant B cell populations. Filtering the genome for overexpressed genes coding for cell membrane-bound proteins/receptors resulted in a hit list of 27 identified genes. Among these, we have focused on the aberrant over expression of CX3CR1, in different types of B cell lymphoma, as compared to non-malignant B cells. We show that CX3CR1, which normally is not expressed on B cells, is expressed both at the mRNA and protein level in several subtypes of lymphoma. CX3CR1 has also shown to be involved in the homing to specific tissues that express the ligand, CX3CL1, in breast and prostate cancer and may thus be involved in dissemination of lymphoma.
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PMID:B cell lymphomas express CX3CR1 a non-B cell lineage adhesion molecule. 1806 Jun 87

Early detection of prostate cancer is problematic due to the lack of a marker that has high diagnostic sensitivity and specificity. The prostate specific antigen (PSA) test, in combination with digital rectal examination, is the gold standard for prostate cancer diagnosis. However, this modality suffers from low specificity. Therefore, specific markers for clinically relevant prostate cancer are needed. Our objective was to proteomically characterize the conditioned media from three human prostate cancer cell lines of differing origin [PC3 (bone metastasis), LNCaP (lymph node metastasis), and 22Rv1 (localized to prostate)] to identify secreted proteins that could serve as novel prostate cancer biomarkers. Each cell line was cultured in triplicate, followed by a bottom-up analysis of the peptides by two-dimensional chromatography and tandem mass spectrometry. Approximately, 12% (329) of the proteins identified were classified as extracellular and 18% (504) as membrane-bound among which were known prostate cancer biomarkers such as PSA and KLK2. To select the most promising candidates for further investigation, tissue specificity, biological function, disease association based on literature searches, and comparison of protein overlap with the proteome of seminal plasma and serum were examined. On the basis of this, four novel candidates, follistatin, chemokine (C-X-C motif) ligand 16, pentraxin 3 and spondin 2, were validated in the serum of patients with and without prostate cancer. The proteins presented in this study represent a comprehensive sampling of the secreted and shed proteins expressed by prostate cancer cells, which may be useful as diagnostic, prognostic or predictive serological markers for prostate cancer.
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PMID:Proteomic analysis of conditioned media from the PC3, LNCaP, and 22Rv1 prostate cancer cell lines: discovery and validation of candidate prostate cancer biomarkers. 1857 23

The tyrosine kinase receptor c-kit and its ligand stem cell factor (SCF) have not been explored in prostate cancer (PC) bone metastasis. Herein, we found that three human PC cell lines and bone marrow stromal cells express a membrane-bound SCF isoform and release a soluble SCF. Bone marrow stromal cells revealed strong expression of c-kit, whereas PC cells showed very low levels of the receptor or did not express it all. Using an experimental model of PC bone metastasis, we found that intraosseous bone tumors formed by otherwise c-kit-negative PC3 cells strongly expressed c-kit, as demonstrated using immunohistochemical and Western blot analyses. Subcutaneous PC3 tumors were, however, c-kit-negative. Both bone and subcutaneous PC3 tumors were positive for SCF. Immunohistochemical analysis of human specimens revealed that the expression frequency of c-kit in epithelial cells was of 5% in benign prostatic hyperplasia, 14% in primary PC, and 40% in PC bone metastases, suggesting an overall trend of increased c-kit expression in clinical PC progression. Stem cell factor expression frequency was more than 80% in all the cases. Our data suggest that the bone microenvironment up-regulates c-kit expression on PC cells, favoring their intraosseous expansion.
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PMID:C-kit and its ligand stem cell factor: potential contribution to prostate cancer bone metastasis. 1871 1

17beta-Hydroxysteroid dehydrogenase type 3 (17beta-HSD3) is expressed at high levels in the testes and seminal vesicles but has also been shown to be present in prostate tissue, suggesting its potential involvement in both gonadal and non-gonadal testosterone biosynthesis. The role of 17beta-HSD3 in testosterone biosynthesis makes this enzyme an attractive molecular target for small molecule inhibitors for the treatment of prostate cancer. Here we report the design of selective inhibitors of 17beta-HSD3 as potential anti-cancer agents. Due to 17beta-HSD3 being a membrane-bound protein a crystal structure is not yet available. A homology model of 17beta-HSD3 has been built to aid structure-based drug design. This model has been used with docking studies to identify a series of lead compounds that may give an insight as to how inhibitors interact with the active site. Compound 1 was identified as a potent selective inhibitor of 17beta-HSD3 with an IC(50)=700nM resulting in the discovery of a novel lead series for further optimisation. Using our homology model as a tool for inhibitor design compound 5 was discovered as a novel potent and selective inhibitor of 17beta-HSD3 with an IC(50) approximately 200nM.
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PMID:The design of novel 17beta-hydroxysteroid dehydrogenase type 3 inhibitors. 1877 69

Six transmembrane epithelial antigen of the prostate 1 (STEAP1) was identified as a prostate-specific cell-surface antigen over-expressed in prostate cancer, and in human cancer cell lines obtained from several other tissues. Its cell surface location in all tumor types analyzed so far, and its absence in most vital organs in humans, turned STEAP1 into a potential target for anti-tumor immunotherapy. This study provides experimental evidence that STEAP1 is also over-expressed in human breast cancer cases, and in normal breast tissue adjacent to breast tumors, where it is localized in the cell membrane of epithelial cells. It is also demonstrated that STEAP1 transcription correlates negatively with estrogen receptor (ER) immunoreactivity, and positively with tumor grading in breast cancer cases. As estrogens are involved in breast cancer onset and progression, the response of STEAP1 to 17beta-estradiol (E2) was investigated in the mammary gland of rats, and in the human breast cancer cell line, MCF-7. These experiments demonstrated that STEAP1 is down-regulated by E2 in both models. The mechanisms underlying the STEAP1 response to E2 in vitro were further investigated in MCF-7 cells, and the results obtained suggest an effect mediated by the membrane-bound ERalpha (mbERalpha).
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PMID:STEAP1 is over-expressed in breast cancer and down-regulated by 17beta-estradiol in MCF-7 cells and in the rat mammary gland. 1895 32

Recent investigations on the effects of phyto-oestrogens on various tissues have revealed that these diverse molecules may improve human health, particularly by protecting against certain chronic diseases. After a brief examination of the food sources, structures, and general cellular actions of the major phyto-oestrogens, current research findings on cardiovascular disease, skeletal tissues, and reproductive cancers are reviewed. Phyto-oestrogen concentrations in blood may be maintained at high levels in those consuming soyabean (Glycine max)-based food daily at several meals and exert their effects on target cells through either genomic effects via the classical oestrogen receptors or non-genomic effects mediated by membrane-bound oestrogen receptors or other cellular proteins. The expression of oestrogen receptor (OR) subtypes alpha (a) and beta (beta) varies across tissues, and cells that preferentially express OR-beta, which may include bone cells, are more likely to respond to phyto-oestrogens. Conversely, reproductive tissues contain relatively more OR-a and may, thus, be differently affected by phyto-oestrogens. Soyabean phyto-oestrogens appear to prevent the progression of atherosclerosis through multiple interactions, including lowering of plasma lipids and lipoproteins, increased vasodilatation and, possibly, decreased activation of blood platelets and vascular smooth muscle cells. However, a favourable impact on cardiovascular disease morbidity and mortality by a soyabean-enriched western-type diet remains to be shown, and unresolved questions remain regarding dose and form of the phyto-oestrogens in relation to risks and benefits. The isoflavones of soyabean have been shown consistently to have bone-retentive effects in animal studies by several investigators using rodent models, although intakes must be above a relatively high threshold level for a lengthy period of time, and little or no extra benefit is observed with intakes above this threshold level. The reports of modest or no effects on prevention of bone loss in human and non-human primate studies respectively, may be due to the limited doses tested so far. The relationship between soyabean-food intake and cancer risk has been more extensively investigated than for any other disease, but with less certainty about the benefits of long-term consumption of phyto-oestrogen-containing foods on prevention of cancer. The observations that breast and prostate cancer rates are lower in Asian countries, where soyabean foods are consumed at high levels, and the high isoflavone content of soyabeans have led to examination of the potential protective effects of phyto-oestrogens. Establishing diet-cancer relationships has proved difficult, in part because of the conflicting data from various studies of effects of soyabean-diets on cancer. Epidemiological evidence, though not impressive, does suggest that soyabean intake reduces breast cancer risk. The isoflavone genistein has a potent effect on breast cancer cells in vitro, and early exposure of animals to genistein has been effective in reducing later development of mammary cancer. Thus, continuous consumption of soyabean foods in early life and adulthood may help explain the low breast cancer mortality rates in Asian countries. Although the evidence for a protective effect against prostate cancer may be slightly more supportive, more research is needed before any firm conclusions can be made about the phyto-oestrogen-cancer linkages.
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PMID:Effects of phyto-oestrogens on tissues. 1908 47

The metalloproteinase ADAM15 is a multi-domain disintegrin protease that is upregulated in a variety of human cancers. ADAM15 mRNA and protein levels are increased in prostate cancer and its expression is significantly increased during metastatic progression. It is likely that ADAM15 supports disease progression differentially through the action of its various functional domains. ADAM15 may downregulate adhesion of tumor cells to the extracellular matrix, reduce cell-cell adhesion, and promote metastasis through the activity of its disintegrin and metalloproteinase domains. Additionally, ADAM15 can influence cell signaling by shedding membrane-bound growth factors and other proteins that interact with receptor tyrosine kinases, leading to receptor activation. There is also evidence supporting a role for ADAM15 in angiogenesis and angioinvasion of tumor cells, which are critical for unrestrained tumor growth and metastatic spread. Given its diverse functions, ADAM15 may represent a pivotal regulatory component of tumor progression, an important target for therapeutic intervention, or emerge as a biomarker of disease progression.
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PMID:The role of the disintegrin metalloproteinase ADAM15 in prostate cancer progression. 1922 65

Two recent papers reveal that the soluble and secreted prostatic acid phosphatase, an enzyme that has long served as a diagnostic marker for prostate cancer, has a membrane-bound splice variant. This enzyme exhibits ecto-5'-nucleotidase activity, is widely distributed, and implicated in the formation of chronic pain. While prostatic acid phosphatase hydrolyzes phosphomonoesters other than 5'-nucleoside monophosphates these novel data suggest that, in addition to ecto-5'-nucleotidase and the alkaline phosphatases, prostatic acid phosphatase must be taken into account in future studies on extracellular adenosine production.
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PMID:Prostatic acid phosphatase, a neglected ectonucleotidase. 1932 80


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