Evaluation of ERG responsive proteome in prostate cancer

Shyh Han Tan; Bungo Furusato; Xueping Fang; Fang He; Ahmed A. Mohamed; Nicholas B. Griner; Kaneeka Sood; Sadhvi Saxena; Shilpa Katta; Denise Young; Yongmei Chen; Taduru Sreenath; Gyorgy Petrovics; Albert Dobi; David G. McLeod; Isabell A. Sesterhenn; Satya Saxena; Shiv Srivastava

doi:10.1002/pros.22731

Evaluation of ERG responsive proteome in prostate cancer

Shyh Han Tan^*, Bungo Furusato, Xueping Fang, Fang He, Ahmed A. Mohamed, Nicholas B. Griner, Kaneeka Sood, Sadhvi Saxena, Shilpa Katta, Denise Young, Yongmei Chen, Taduru Sreenath, Gyorgy Petrovics, Albert Dobi, David G. McLeod, Isabell A. Sesterhenn, Satya Saxena, Shiv Srivastava

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

BACKGROUND Gene fusion between TMPRSS2 promoter and the ERG 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. METHODS Global proteome analysis was performed by using ERG (+) and ERG (-) CaP cells isolated by ERG immunohistochemistry defined laser capture microdissection and by using TMPRSS2-ERG positive VCaP cells treated with ERG and control siRNA. RESULTS 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 Myosin VI and Monoamine oxidase A were positively and negatively correlated to ERG expression, respectively. CONCLUSIONS 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.

Original language	English
Pages (from-to)	70-89
Number of pages	20
Journal	Prostate
Volume	74
Issue number	1
DOIs	https://doi.org/10.1002/pros.22731
State	Published - Jan 2014
Externally published	Yes

Keywords

ERG
MAOA
actin and cytoskeletal reorganization
myosin VI
proteomics

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10.1002/pros.22731

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@article{6553884a9f2b4b9c95cf2946d4da6f6a,

title = "Evaluation of ERG responsive proteome in prostate cancer",

abstract = "BACKGROUND Gene fusion between TMPRSS2 promoter and the ERG 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. METHODS Global proteome analysis was performed by using ERG (+) and ERG (-) CaP cells isolated by ERG immunohistochemistry defined laser capture microdissection and by using TMPRSS2-ERG positive VCaP cells treated with ERG and control siRNA. RESULTS 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 Myosin VI and Monoamine oxidase A were positively and negatively correlated to ERG expression, respectively. CONCLUSIONS 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.",

keywords = "ERG, MAOA, actin and cytoskeletal reorganization, myosin VI, proteomics",

author = "Tan, {Shyh Han} and Bungo Furusato and Xueping Fang and Fang He and Mohamed, {Ahmed A.} and Griner, {Nicholas B.} and Kaneeka Sood and Sadhvi Saxena and Shilpa Katta and Denise Young and Yongmei Chen and Taduru Sreenath and Gyorgy Petrovics and Albert Dobi and McLeod, {David G.} and Sesterhenn, {Isabell A.} and Satya Saxena and Shiv Srivastava",

year = "2014",

month = jan,

doi = "10.1002/pros.22731",

language = "English",

volume = "74",

pages = "70--89",

journal = "Prostate",

issn = "0270-4137",

number = "1",

}

TY - JOUR

T1 - Evaluation of ERG responsive proteome in prostate cancer

AU - Tan, Shyh Han

AU - Furusato, Bungo

AU - Fang, Xueping

AU - He, Fang

AU - Mohamed, Ahmed A.

AU - Griner, Nicholas B.

AU - Sood, Kaneeka

AU - Saxena, Sadhvi

AU - Katta, Shilpa

AU - Young, Denise

AU - Chen, Yongmei

AU - Sreenath, Taduru

AU - Petrovics, Gyorgy

AU - Dobi, Albert

AU - McLeod, David G.

AU - Sesterhenn, Isabell A.

AU - Saxena, Satya

AU - Srivastava, Shiv

PY - 2014/1

Y1 - 2014/1

N2 - BACKGROUND Gene fusion between TMPRSS2 promoter and the ERG 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. METHODS Global proteome analysis was performed by using ERG (+) and ERG (-) CaP cells isolated by ERG immunohistochemistry defined laser capture microdissection and by using TMPRSS2-ERG positive VCaP cells treated with ERG and control siRNA. RESULTS 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 Myosin VI and Monoamine oxidase A were positively and negatively correlated to ERG expression, respectively. CONCLUSIONS 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.

AB - BACKGROUND Gene fusion between TMPRSS2 promoter and the ERG 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. METHODS Global proteome analysis was performed by using ERG (+) and ERG (-) CaP cells isolated by ERG immunohistochemistry defined laser capture microdissection and by using TMPRSS2-ERG positive VCaP cells treated with ERG and control siRNA. RESULTS 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 Myosin VI and Monoamine oxidase A were positively and negatively correlated to ERG expression, respectively. CONCLUSIONS 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.

KW - ERG

KW - MAOA

KW - actin and cytoskeletal reorganization

KW - myosin VI

KW - proteomics

UR - http://www.scopus.com/inward/record.url?scp=84890125967&partnerID=8YFLogxK

U2 - 10.1002/pros.22731

DO - 10.1002/pros.22731

M3 - Article

C2 - 24115221

AN - SCOPUS:84890125967

SN - 0270-4137

VL - 74

SP - 70

EP - 89

JO - Prostate

JF - Prostate

IS - 1

ER -

Evaluation of ERG responsive proteome in prostate cancer

Abstract

Keywords

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