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.
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.
Authors: Young Ah Goo; Alvin Y Liu; Soyoung Ryu; Scott A Shaffer; Lars Malmström; Laura Page; Liem T Nguyen; Catalin E Doneanu; David R Goodlett Journal: Prostate Date: 2009-01-01 Impact factor: 4.104
Authors: Amjad P Khan; Laila M Poisson; Vadiraja B Bhat; Damian Fermin; Rong Zhao; Shanker Kalyana-Sundaram; George Michailidis; Alexey I Nesvizhskii; Gilbert S Omenn; Arul M Chinnaiyan; Arun Sreekumar Journal: Mol Cell Proteomics Date: 2009-11-09 Impact factor: 5.911
Authors: Ying Hu; Albert Dobi; Taduru Sreenath; Christopher Cook; Atekelt Y Tadase; Lakshmi Ravindranath; Jennifer Cullen; Bungo Furusato; Yongmei Chen; Rajesh L Thangapazham; Ahmed Mohamed; Chen Sun; Isabell A Sesterhenn; David G McLeod; Gyorgy Petrovics; Shiv Srivastava Journal: Clin Cancer Res Date: 2008-08-01 Impact factor: 12.531
Authors: Donald J Johann; Jaime Rodriguez-Canales; Sumana Mukherjee; DaRue A Prieto; Jeffrey C Hanson; Michael Emmert-Buck; Josip Blonder Journal: J Proteome Res Date: 2009-05 Impact factor: 4.466
Authors: Xueping Fang; Weijie Wang; Li Yang; Krish Chandrasekaran; Tibor Kristian; Brian M Balgley; Cheng S Lee Journal: Electrophoresis Date: 2008-05 Impact factor: 3.535
Authors: Shona H Lang; Catherine Hyde; Ian N Reid; Ian S Hitchcock; Claire A Hart; A A Gordon Bryden; Jean-Marie Villette; Michael J Stower; Norman J Maitland Journal: Prostate Date: 2002-09-01 Impact factor: 4.104
Authors: Charles E Massie; Boris Adryan; Nuno L Barbosa-Morais; Andy G Lynch; Maxine G Tran; David E Neal; Ian G Mills Journal: EMBO Rep Date: 2007-08-17 Impact factor: 8.807
Authors: Nicholas B Griner; Denise Young; Pankaj Chaudhary; Ahmed A Mohamed; Wei Huang; Yongmei Chen; Taduru Sreenath; Albert Dobi; Gyorgy Petrovics; Jamboor K Vishwanatha; Isabell A Sesterhenn; Shiv Srivastava; Shyh-Han Tan Journal: Mol Cancer Res Date: 2014-10-24 Impact factor: 5.852
Authors: Carlos D Cruz-Hernández; Marian Cruz-Burgos; Sergio A Cortés-Ramírez; Alberto Losada-García; Ignacio Camacho-Arroyo; Patricia García-López; Elizabeth Langley; Vanessa González-Covarrubias; Monserrat Llaguno-Munive; Martha E Albino-Sánchez; José L Cruz-Colín; Carlos Pérez-Plasencia; Fredy O Beltrán-Anaya; Mauricio Rodríguez-Dorantes Journal: Cancer Cell Int Date: 2020-07-16 Impact factor: 5.722
Authors: Asmus Heumann; Nina Heinemann; Claudia Hube-Magg; Dagmar S Lang; Katharina Grupp; Martina Kluth; Sarah Minner; Christina Möller-Koop; Markus Graefen; Hans Heinzer; Maria Christina Tsourlakis; Waldemar Wilczak; Corinna Wittmer; Frank Jacobsen; Hartwig Huland; Ronald Simon; Thorsten Schlomm; Guido Sauter; Stefan Steurer; Patrick Lebok; Andrea Hinsch Journal: BMC Cancer Date: 2018-01-05 Impact factor: 4.430