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)

Prostate cancer is the second leading cause of cancer related deaths in men in the United States and for many years the treatment results for metastatic prostate cancer have been disappointing. Our previous studies have shown that genistein elicits pleiotropic effects on prostate cancer cells; however, its role in invasion and metastasis has not been fully elucidated. In order to better understand the precise molecular mechanism(s) by which genistein exerts its effects on PC3 cells, we have utilized cDNA microarray to interrogate 12558 known genes to determine the gene expression profile altered by genistein treatment. We found a total of 832 genes which showed >2-fold change after genistein treatment. Among these genes, we found down-regulation of 11 genes (MMP-9, protease M, uPAR, VEGF, neuropilin, TSP, BPGF, LPA, TGF-beta2, TSP-1, PAR-2) and up-regulation of two genes (connective tissue growth factor, connective tissue activation peptide), which are related to angiogenesis, tumor cell invasion and metastasis. Reverse transcription-polymerase chain reaction, Western blot, and zymographic analysis were conducted to confirm the data of microarray at the level of mRNA, protein, and biological function. The results were in direct agreement with the microarray data. From these results, we conclude that genistein down-regulates the transcription and translation of genes critically involved in the control of angiogenesis, tumor cell invasion and metastasis, suggesting the possible therapeutic role of genistein for metastatic prostate cancer. Thus, genistein-induced alternations of gene expressions may be exploited for devising chemopreventive or therapeutic strategies, particularly for chemosensitization of metastatic prostate cancer to existing chemotherapeutic agents.
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PMID:Down-regulation of invasion and angiogenesis-related genes identified by cDNA microarray analysis of PC3 prostate cancer cells treated with genistein. 1221 85

Thrombospondin is a potent inhibitor of angiogenesis and might therefore be important in controlling tumour growth. TSP interacts with a number of proteases and receptors and in this way inhibits stimulation of angiogenesis. An earlier study showed that thrombospondin is expressed in benign prostatic hyperplasia (BPH) and high-grade prostatic intraepithelial neoplasia (PIN) but is absent in prostate cancer. The present study was therefore designed to evaluate the expression of thrombospondin 1 and 2 (TSP-1, TSP-2), TSP receptors CD36 and CD47, and matrix-metalloproteases 2 and 9 (MMP-, MMP-9) in a rat prostate cancer model. By using immunohistochemistry, Western blot, and real-time PCR the expression patterns of TSP-1, TSP-2, CD36, CD47, MMP-2, and MMP-9 were investigated in normal rat prostate tissue and five malignant Dunning sublines tissue. TSP-1 mRNA levels were decreased in all tumours compared with normal prostate. However, there was no difference in expression of TSP-2 and CD36 mRNA in these samples. MMP-2 was increased with malignancy, but no expression of MMP-9 was seen. The CD47 receptor did slightly increase with malignancy except for H3327. The results showed that thrombospondin is expressed in normal prostate but not in prostate tumours in a rat model. Simultaneously, MMP-2 expression increases with malignancy.
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PMID:Thrombospondins, metallo proteases and thrombospondin receptors messenger RNA and protein expression in different tumour sublines of the Dunning prostate cancer model. 1607 2

The aim of this study was to investigate the relationship between microvessel density (MVD), positive and negative angiogenic factors, and established prognostic factors in prostate cancer (PC), and, to clarify the effect of angiogenic factors to angiogenesis. The vascularization of neoplastic, non-neoplastic prostate tissue was determined by CD34 immunostaining. Angiogenetic mediators VEGF, bFGF, TSP-1, and p53 were studied by immunohistochemistry. Neovascularization and p53, VEGF, and TSP-1 expressions of tumorous tissue were higher than non-tumorous tissue. The bFGF expression in these tissues was not different. The p53 expression was not correlated with the expressions of VEGF, bFGF, and TSP-1 in PC. Our results demonstrate a significant increase in MVD, VEGF, TSP-1, and p53 expressions in prostate tumorigenesis. The pretreatment sPSA was the only parameter demonstrating significant correlation with tumor grade and may have a value in the prediction of aggressive tumor behavior in PC.
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PMID:Microvessel density and regulators of angiogenesis in malignant and nonmalignant prostate tissue. 1718 Apr 40

Angiogenesis is an important process for tumor growth and progression of various solid tumors including urological cancers. Thrombospondins (TSPs), especially TSP-1, are representative "anti"-angiogenic molecules and many studies have clarified their pathological role and clinical significance in vivo and in vitro. In fact, TSP-1 expression is associated with clinicopathological features and prognosis in many types of cancers. However, TSP-1 is a multi-functional protein and its biological activities vary according to the specific tumor environments. Consequently, there is no general agreement on its cancer-related function in urological cancers, and detailed information regarding regulative mechanisms is essential for a better understanding of its therapeutic effects and prognostic values. Various "suppressor genes" and "oncogenes" are known to be regulators and TSP-1-related factors under physiological and pathological conditions. In addition, various types of fragments derived from TSP-1 exist in a given tissue microenvironment and TSP-1 derived-peptides have specific activities. However, a detailed pathological function in human cancer tissues is not still understood. This review will focus on the pathological roles and clinical significance of TSP-1 in urological cancers, including prostate cancer, renal cell carcinoma, and urothelial cancer. In addition, special attention is paid to TSP-1-derived peptide and TSP-1-based therapy for malignancies.
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PMID:Thrombospondin-1 in urological cancer: pathological role, clinical significance, and therapeutic prospects. 2374 12