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Long noncoding RNA-mediated activation of androgen receptor in prostate cancer

Asian Journal of Andrology 2014年第3期16卷 418-419页

作者： gyorgy petrovics Shiv Srivastava Center for Prostate Disease Research Department ofSurgery Uniformed Services University of the HealthSciences Maryland USA.

Remarkable progress has been made in molecular characterization of prostate cancer （PCa） with continued innovations in high throughput technologies evaluating human cancer？-3 Since the completion of the Human Genome Project it has been estimated that only about 1.5%-2% of our genome codes for proteins. Various genome-wide approaches, e.g. the ENCODE project, revealed that a much larger percent of the genome is transcribed as non-protein coding （nc） RNA, including long noncoding （lnc） RNA （over 200bps long）. Although the biological roles of IncRNA （the ＇dark matter of the genome＇） are not nearly as well-understood as the protein coding mRNAs, it is increasingly clear that they play important roles in almost every aspects of biology, including cancer biology.4＇5 This is exemplified by recent genome-wide association studies revealing that over 80% of cancer-associated single nucleotide polymorphisms （SNPs） are in noncoding regions of the genome.

关键词： Remarkable progress androgen receptor characterization

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Highlights from the prostate cancer genome report

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Asian Journal of Andrology 2011年第5期13卷 659-660页

作者： Shyh-Han Tan gyorgy petrovics Shiv Srivastava Center for Prostate Disease Research Department of Surgery Uniformed Services University of the Health Sciences Rockville MD 20852 USA

Prostate cancer （CAP） is the second most frequently diagnosed cancer of men worldwide （899 000 new cases, 13.6% of the total）, with nearly 75% of the registered cases occurring in developed countries （644 000 cases）.1 Blood prostate-specific antigen test has revolutionized the early detection of CaP and organ-confined CaP is effectively managed by state-of-the-art treatments including radical prostatectomy or radiation therapy.2 In the past decade, tremendous progress has also been made in our understanding of the biology and common genomic alterations in CaP.3＇4 New molecular marker assays have promise in improving CaP diagnosis.5-8 Despite these advances, major challenges remain with our ability to distinguish indolent cancers from the more aggressive cancers detected early due to widely used prostate-specific antigen test. Furthermore, development of molecular stratification of CaP for targeted and more effective therapies is critically needed.

关键词： Highlights effective therapies

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Quantitative analysis of a panel of gene expression in prostate cancer——with emphasis on NPY expression analysis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2007年第12期8卷 853-859页

作者： LIU Ai-jun FURUSATO Bungo RAVINDRANATH Lakshmi CHEN Yong-mei SRIKANTAN Vasanta MCLEOD David G. petrovics gyorgy SRIVASTAVA Shiv Department of Pathology Chinese PLA General Hospital Beo＇ing 100853 China Center for Prostate Disease Research Uniformed Services University of the Health Sciences Rockville MD 20852 USA Urology Service Walter Reed Army Medical Center Washington DC 20307 USA

Objective： To investigate molecular alterations associating with prostate carcinoma progression and potentially provide information toward more accurate prognosis/diagnosis. Methods： A set of laser captured microdissected （LCM） specimens from 300 prostate cancer （PCa） patients undergoing radical prostatectomy （RP） were defined. Ten patients representing ＂aggressive＂ PCa, and 10 representing ＂non-aggressive＂ PCa were selected based on prostate-specific antigen （PSA） recurrence, Gleason score, pathological stage and tumor cell differentiation, with matched patient age and race between the two groups. Normal and neoplastic prostate epithelial cells were collected with LCM from frozen tissue slides obtained from the RP specimens. The expressions of a panel of genes, including NPY, PTEN, AR, AMACR, DD3, and GSTP1, were measured by quantitative real-time RT-PCR （TaqMan）, and correlation was analyzed with clinicopathological features. Results： The expressions of AMACR and DD3 were consistently up-regulated in cancer cells compared to benign prostate epithelial cells in all PCa patients, whereas GSTP1 expression was down regulated in each patient. NPY, PTEN and AR exhibited a striking difference in their expression patterns between aggressive and non-aggressive PCas （P=0.0203, 0.0284, and 0.0378, respectively, Wilcoxon rank sum test）. The lower expression of NPY showed association with ＂aggressive＂ PCas based on a larger PCa patient cohort analysis （P=0.0037, univariate generalized linear model （GLM） analysis）. Conclusion： Despite widely noted heterogeneous nature of PCa, gene expression alterations ofAM,4CR, DD3, and GSTP1 in LCM-derived PCa epithelial cells suggest for common underlying mechanisms in the initiation of PCa. Lower NPY expression level is significantly associated with more aggressive clinical behavior of PCa; PTEN and AR may have potential in defining PCa with aggressive clinical behavior. Studies along these lines have potential to define PCa-associated gen

关键词： Prostate cancer NPY expression Quantitative real-time reverse-transcript polymerase chain reaction (RT-PCR)

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Quantitative Analysis of a Panel of Gene Expression in Matched Benign and Neoplastic Prostate Epithelial Cells from Patients with“Aggressive”and“Nonaggressive”Prostate Cancer

Quantitative Analysis of a Panel of Gene Expression in Match...

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中华医学会病理学分会2005年学术年会

作者：刘爱军 Bungo Furusato Lakshmi Ravindranath Syed Shaheduzzaman Vasantha Srikantan Iabell A.Sesterhenn David G.McLeod Judd W.Moul Shiv Srivastava gyorgy petrovics Centerfor Prostate Disease Research Uniformed Services University of the Health Sciences Center for Prostate Disease Research Uniformed Services University of the Health Sciences Department of Genitourinary Pathology Armed Forces Institute of Pathology Urology Service Walter Reed Army Medical Center Center for Prostate Disease Research Uniformed Services University of the Health Sciences Urology ServiceWalter Reed Army Medical Center

Prostate cancer (CaP) is a complex, multifactorialdisease with heterogeneous tumor types, making the prediction of the clinical course for individual CaP patients a challenge. To better understand the molecular basis of CaP and potentially provide information toward more accurate prognosis/diagnosis, we have defined a set of laser capture microdissected (LCM) specimens that are being used for quantitative parallel expression analysis of a panel of genes frequently altered in CaP. Experimental Design: From 300 CaP patients undergo-

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Frequent Expression Alterations of ETS Related Gene-1(ERG1)in Prostate Cancer Transcriptome Reveal Diagnostic and Prognostic Biomarker Potential

Frequent Expression Alterations of ETS Related Gene-1(ERG1)i...

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中华医学会病理学分会2005年学术年会

作者：刘爱军 gyorgy petrovics Syed Shaheduzzaman Bungo Furasato Martin Nau Lakshmi Ravindranath Albert Dobi Vasantha Srikantan Isabell A Sesterhenn David G McLeod Maryanne Vahey Judd W Moul Shiv Srivastava Centerfor Prostate Disease Research US Military Cancer InstituteUniformed Services University Center for Prostate Disease Research US Military Cancer InstituteUniformed Services University Department of Genitourinary Pathology Armed Forces Institute of Pathology Laboratory of Functional Genomics Walter Reed Army Institute of Research Urology Service Walter Reed Army Medical Center

Transcription factors encoded by the ETS family of genes are central in integrating signals that regulate cell growth and differentiation, stress responses and tumorigenesis. This study, using laser microdissected paired benign and malignant prostate epithelial cells from prostate cancer (CaP) patients (n=114), identifies ERG, a member of the ETS transcription factor family, as the most frequently overexpressed poto-oncogene in the transcriptome of malignant prostate epithelial cells. Combined quantitative expression analysis of ERG with two other genes commonly overexpressed in CaP, AMACR and DD3, revealed overexpression of at least one of these three genes in virtually all cancer specimen (54 of 55). Therefore,

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