Evaluation of ERG responsive proteome in prostate cancer. Issue 1 (21st September 2013)

• Record Type: Journal Article
• Authors: Tan, Shyh‐Han; Furusato, Bungo; Fang, Xueping; He, Fang; Mohamed, Ahmed A.; Griner, Nicholas B.; Sood, Kaneeka; Saxena, Sadhvi; Katta, Shilpa; Young, Denise; Chen, Yongmei; Sreenath, Taduru; Petrovics, Gyorgy; Dobi, Albert; McLeod, David G.; Sesterhenn, Isabell A.; Saxena, Satya; Srivastava, Shiv
• Is Part Of: Prostate. Volume 74:Issue 1(2014)
• Page Start: 70
• Page End: 89
• Publication Date: 2013-09-21
• Subjects: Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.22731
• Languages: English
• ISSNs: 0270-4137

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="pros22731-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Gene fusion between <italic>TMPRSS2</italic> promoter and the <italic>ERG</italic> proto‐oncogene is a major genomic alteration found in over half of prostate cancers (CaP), which leads to aberrant androgen dependent ERG expression. Despite extensive analysis for the biological functions of ERG in CaP, there is no systematic evaluation of the ERG responsive proteome (ERP). ERP has the potential to define new biomarkers and therapeutic targets for prostate tumors stratified by ERG expression.</p> </sec> <sec id="pros22731-sec-0002" sec-type="section"> <title>METHODS</title> <p>Global proteome analysis was performed by using ERG (+) and ERG (−) CaP cells isolated by ERG immunohistochemistry defined laser capture microdissection and by using <italic>TMPRSS2‐ERG</italic> positive VCaP cells treated with <italic>ERG</italic> and control siRNA.</p> </sec> <sec id="pros22731-sec-0003" sec-type="section"> <title>RESULTS</title> <p>We identified 1, 196 and 2, 190 unique proteins stratified by ERG status from prostate tumors and VCaP cells, respectively. Comparative analysis of these two proteomes identified 330 concordantly regulated proteins characterizing enrichment of pathways modulating cytoskeletal and actin reorganization, cell migration, protein biosynthesis, and proteasome and ER‐associated protein degradation. ERPs unique for ERG (+) tumors reveal enrichment for cell growth and survival pathways while proteasome and redox function pathways were enriched in ERPs unique for ERG (−) tumors. Meta‐analysis of ERPs against CaP gene expression data revealed that <italic>Myosin VI</italic> and <italic>Monoamine oxidase A</italic> were positively and negatively correlated to <italic>ERG</italic> expression, respectively.</p> </sec> <sec id="pros22731-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>This study delineates the global proteome for prostate tumors stratified by ERG expression status. The ERP data confirm the functions of ERG in inhibiting cell differentiation and activating cell growth, and identify potentially novel biomarkers and therapeutic targets. <italic>Prostate 74:70–89, 2014</italic>. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>