Antinuclear autoantibodies in prostate cancer: Immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis

BACKGROUND Cancer patients produce autoantibodies to self‐proteins called tumor‐associated antigens (TAA). These autoantibodies represent potentially valuable tools for identifying novel biomarkers and therapeutic targets. This study was designed to identify TAA in prostate cancer (PCa). METHODS Ser...

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Veröffentlicht in:The Prostate 2005-01, Vol.62 (1), p.14-26
Hauptverfasser: Daniels, Tracy, Zhang, Jianying, Gutierrez, Israel, Elliot, Max L., Yamada, Brian, Heeb, Mary Jo, Sheets, Shaun M., Wu, Xiwei, Casiano, Carlos A.
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container_end_page 26
container_issue 1
container_start_page 14
container_title The Prostate
container_volume 62
creator Daniels, Tracy
Zhang, Jianying
Gutierrez, Israel
Elliot, Max L.
Yamada, Brian
Heeb, Mary Jo
Sheets, Shaun M.
Wu, Xiwei
Casiano, Carlos A.
description BACKGROUND Cancer patients produce autoantibodies to self‐proteins called tumor‐associated antigens (TAA). These autoantibodies represent potentially valuable tools for identifying novel biomarkers and therapeutic targets. This study was designed to identify TAA in prostate cancer (PCa). METHODS Serum autoantibodies to the survival protein lens epithelium‐derived growth factor p75 (LEDGF/p75) were detected by immunofluorescence microscopy, ELISA, and immunoblotting. Expression of LEDGF/p75 in prostate cells and tumors was evaluated by immunoblotting or immunohistochemistry. Apoptotic cleavage of LEDGF/p75 was detected by immunoblotting. RESULTS Anti‐LEDGF/p75 autoantibodies were detected by ELISA in 18.4% of PCa patients and 5.5% of matched controls (P 
doi_str_mv 10.1002/pros.20112
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These autoantibodies represent potentially valuable tools for identifying novel biomarkers and therapeutic targets. This study was designed to identify TAA in prostate cancer (PCa). METHODS Serum autoantibodies to the survival protein lens epithelium‐derived growth factor p75 (LEDGF/p75) were detected by immunofluorescence microscopy, ELISA, and immunoblotting. Expression of LEDGF/p75 in prostate cells and tumors was evaluated by immunoblotting or immunohistochemistry. Apoptotic cleavage of LEDGF/p75 was detected by immunoblotting. RESULTS Anti‐LEDGF/p75 autoantibodies were detected by ELISA in 18.4% of PCa patients and 5.5% of matched controls (P &lt; 0.001) but not in patients with benign prostatic hyperplasia (BPH). LEDGF/p75 expression was detected in 93% of prostate tumors but not in normal prostate. Strong expression of the protein was observed in 61% of prostate tumors. Moderate to high expression was also detected in BPH tissue. Cleavage of LEDGF/p75 was detected in apoptotic prostate cells. CONCLUSIONS The high expression of LEDGF/p75 in prostate tumors and BPH could be induced by inflammation and oxidative stress. LEDGF/p75 cleavage fragments generated during prostate tumor cell death might trigger autoantibodies under inflammatory conditions in certain patients. © 2004 Wiley‐Liss, Inc.</description><identifier>ISSN: 0270-4137</identifier><identifier>EISSN: 1097-0045</identifier><identifier>DOI: 10.1002/pros.20112</identifier><identifier>PMID: 15389814</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adenocarcinoma - immunology ; Adenocarcinoma - pathology ; Aged ; Aged, 80 and over ; Antibodies, Antinuclear - immunology ; Antigens, Neoplasm - immunology ; apoptosis ; Apoptosis - immunology ; autoantibodies ; Autoantibodies - immunology ; Biomarkers, Tumor - immunology ; Cell Line, Tumor ; Humans ; inflammation ; Intercellular Signaling Peptides and Proteins - immunology ; LEDGF/p75 ; Male ; Middle Aged ; oxidative stress ; prostate cancer ; Prostatic Neoplasms - immunology ; Prostatic Neoplasms - pathology ; Rhabdomyosarcoma, Embryonal - immunology ; tumor-associated antigens</subject><ispartof>The Prostate, 2005-01, Vol.62 (1), p.14-26</ispartof><rights>Copyright © 2004 Wiley‐Liss, Inc.</rights><rights>Copyright 2004 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3652-6846ed5490d7356a7d31ff216112ac763d2f91a2679b8d39bb4c24573b2203173</citedby><cites>FETCH-LOGICAL-c3652-6846ed5490d7356a7d31ff216112ac763d2f91a2679b8d39bb4c24573b2203173</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpros.20112$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpros.20112$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15389814$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Daniels, Tracy</creatorcontrib><creatorcontrib>Zhang, Jianying</creatorcontrib><creatorcontrib>Gutierrez, Israel</creatorcontrib><creatorcontrib>Elliot, Max L.</creatorcontrib><creatorcontrib>Yamada, Brian</creatorcontrib><creatorcontrib>Heeb, Mary Jo</creatorcontrib><creatorcontrib>Sheets, Shaun M.</creatorcontrib><creatorcontrib>Wu, Xiwei</creatorcontrib><creatorcontrib>Casiano, Carlos A.</creatorcontrib><title>Antinuclear autoantibodies in prostate cancer: Immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis</title><title>The Prostate</title><addtitle>Prostate</addtitle><description>BACKGROUND Cancer patients produce autoantibodies to self‐proteins called tumor‐associated antigens (TAA). These autoantibodies represent potentially valuable tools for identifying novel biomarkers and therapeutic targets. This study was designed to identify TAA in prostate cancer (PCa). METHODS Serum autoantibodies to the survival protein lens epithelium‐derived growth factor p75 (LEDGF/p75) were detected by immunofluorescence microscopy, ELISA, and immunoblotting. Expression of LEDGF/p75 in prostate cells and tumors was evaluated by immunoblotting or immunohistochemistry. Apoptotic cleavage of LEDGF/p75 was detected by immunoblotting. RESULTS Anti‐LEDGF/p75 autoantibodies were detected by ELISA in 18.4% of PCa patients and 5.5% of matched controls (P &lt; 0.001) but not in patients with benign prostatic hyperplasia (BPH). LEDGF/p75 expression was detected in 93% of prostate tumors but not in normal prostate. Strong expression of the protein was observed in 61% of prostate tumors. Moderate to high expression was also detected in BPH tissue. Cleavage of LEDGF/p75 was detected in apoptotic prostate cells. CONCLUSIONS The high expression of LEDGF/p75 in prostate tumors and BPH could be induced by inflammation and oxidative stress. LEDGF/p75 cleavage fragments generated during prostate tumor cell death might trigger autoantibodies under inflammatory conditions in certain patients. © 2004 Wiley‐Liss, Inc.</description><subject>Adenocarcinoma - immunology</subject><subject>Adenocarcinoma - pathology</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antibodies, Antinuclear - immunology</subject><subject>Antigens, Neoplasm - immunology</subject><subject>apoptosis</subject><subject>Apoptosis - immunology</subject><subject>autoantibodies</subject><subject>Autoantibodies - immunology</subject><subject>Biomarkers, Tumor - immunology</subject><subject>Cell Line, Tumor</subject><subject>Humans</subject><subject>inflammation</subject><subject>Intercellular Signaling Peptides and Proteins - immunology</subject><subject>LEDGF/p75</subject><subject>Male</subject><subject>Middle Aged</subject><subject>oxidative stress</subject><subject>prostate cancer</subject><subject>Prostatic Neoplasms - immunology</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Rhabdomyosarcoma, Embryonal - immunology</subject><subject>tumor-associated antigens</subject><issn>0270-4137</issn><issn>1097-0045</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctu1DAUhi0EotPChgdAXrFApPUljhN21dAZKkYUFRBLy4lPWkNu-DLtPApvi8MMIDasLMvf__lcEHpGySklhJ1NbvSnjFDKHqAFJZXMCMnFQ7QgTJIsp1weoWPvvxKScMIeoyMqeFmVNF-gH-dDsENsOtAO6xhGne71aCx4bAc8q4MOgBs9NOBe48u-j4MNOxxGvLl4s16dTVK8whr76LZ2q7s5EiBFb-3NbbfDcD858B7MP7oQ-9F5rAeD56-36dlEZ4cbrKdxCqO3_gl61OrOw9PDeYI-ry4-Ld9mm6v15fJ8kzW8ECwryrwAI_KKGMlFoaXhtG0ZLdI4dCMLblhbUc0KWdWl4VVd5w3LheQ1Y4RTyU_Qi703Ffc9gg-qt76BrtMDjNGrQjIhWFUl8OUebFIX3kGrJmd77XaKEjUvQs3tqV-LSPDzgzXWPZi_6GHyCaB74M52sPuPSn24vvr4W5rtM9YHuP-T0e5bqpJLob68X6vy3XpJr9lKSf4T352kTw</recordid><startdate>20050101</startdate><enddate>20050101</enddate><creator>Daniels, Tracy</creator><creator>Zhang, Jianying</creator><creator>Gutierrez, Israel</creator><creator>Elliot, Max L.</creator><creator>Yamada, Brian</creator><creator>Heeb, Mary Jo</creator><creator>Sheets, Shaun M.</creator><creator>Wu, Xiwei</creator><creator>Casiano, Carlos A.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20050101</creationdate><title>Antinuclear autoantibodies in prostate cancer: Immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis</title><author>Daniels, Tracy ; Zhang, Jianying ; Gutierrez, Israel ; Elliot, Max L. ; Yamada, Brian ; Heeb, Mary Jo ; Sheets, Shaun M. ; Wu, Xiwei ; Casiano, Carlos A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3652-6846ed5490d7356a7d31ff216112ac763d2f91a2679b8d39bb4c24573b2203173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adenocarcinoma - immunology</topic><topic>Adenocarcinoma - pathology</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antibodies, Antinuclear - immunology</topic><topic>Antigens, Neoplasm - immunology</topic><topic>apoptosis</topic><topic>Apoptosis - immunology</topic><topic>autoantibodies</topic><topic>Autoantibodies - immunology</topic><topic>Biomarkers, Tumor - immunology</topic><topic>Cell Line, Tumor</topic><topic>Humans</topic><topic>inflammation</topic><topic>Intercellular Signaling Peptides and Proteins - immunology</topic><topic>LEDGF/p75</topic><topic>Male</topic><topic>Middle Aged</topic><topic>oxidative stress</topic><topic>prostate cancer</topic><topic>Prostatic Neoplasms - immunology</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Rhabdomyosarcoma, Embryonal - immunology</topic><topic>tumor-associated antigens</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Daniels, Tracy</creatorcontrib><creatorcontrib>Zhang, Jianying</creatorcontrib><creatorcontrib>Gutierrez, Israel</creatorcontrib><creatorcontrib>Elliot, Max L.</creatorcontrib><creatorcontrib>Yamada, Brian</creatorcontrib><creatorcontrib>Heeb, Mary Jo</creatorcontrib><creatorcontrib>Sheets, Shaun M.</creatorcontrib><creatorcontrib>Wu, Xiwei</creatorcontrib><creatorcontrib>Casiano, Carlos A.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Prostate</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Daniels, Tracy</au><au>Zhang, Jianying</au><au>Gutierrez, Israel</au><au>Elliot, Max L.</au><au>Yamada, Brian</au><au>Heeb, Mary Jo</au><au>Sheets, Shaun M.</au><au>Wu, Xiwei</au><au>Casiano, Carlos A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antinuclear autoantibodies in prostate cancer: Immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis</atitle><jtitle>The Prostate</jtitle><addtitle>Prostate</addtitle><date>2005-01-01</date><risdate>2005</risdate><volume>62</volume><issue>1</issue><spage>14</spage><epage>26</epage><pages>14-26</pages><issn>0270-4137</issn><eissn>1097-0045</eissn><abstract>BACKGROUND Cancer patients produce autoantibodies to self‐proteins called tumor‐associated antigens (TAA). These autoantibodies represent potentially valuable tools for identifying novel biomarkers and therapeutic targets. This study was designed to identify TAA in prostate cancer (PCa). METHODS Serum autoantibodies to the survival protein lens epithelium‐derived growth factor p75 (LEDGF/p75) were detected by immunofluorescence microscopy, ELISA, and immunoblotting. Expression of LEDGF/p75 in prostate cells and tumors was evaluated by immunoblotting or immunohistochemistry. Apoptotic cleavage of LEDGF/p75 was detected by immunoblotting. RESULTS Anti‐LEDGF/p75 autoantibodies were detected by ELISA in 18.4% of PCa patients and 5.5% of matched controls (P &lt; 0.001) but not in patients with benign prostatic hyperplasia (BPH). LEDGF/p75 expression was detected in 93% of prostate tumors but not in normal prostate. Strong expression of the protein was observed in 61% of prostate tumors. Moderate to high expression was also detected in BPH tissue. Cleavage of LEDGF/p75 was detected in apoptotic prostate cells. CONCLUSIONS The high expression of LEDGF/p75 in prostate tumors and BPH could be induced by inflammation and oxidative stress. LEDGF/p75 cleavage fragments generated during prostate tumor cell death might trigger autoantibodies under inflammatory conditions in certain patients. © 2004 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>15389814</pmid><doi>10.1002/pros.20112</doi><tpages>13</tpages></addata></record>
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subjects Adenocarcinoma - immunology
Adenocarcinoma - pathology
Aged
Aged, 80 and over
Antibodies, Antinuclear - immunology
Antigens, Neoplasm - immunology
apoptosis
Apoptosis - immunology
autoantibodies
Autoantibodies - immunology
Biomarkers, Tumor - immunology
Cell Line, Tumor
Humans
inflammation
Intercellular Signaling Peptides and Proteins - immunology
LEDGF/p75
Male
Middle Aged
oxidative stress
prostate cancer
Prostatic Neoplasms - immunology
Prostatic Neoplasms - pathology
Rhabdomyosarcoma, Embryonal - immunology
tumor-associated antigens
title Antinuclear autoantibodies in prostate cancer: Immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis
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