The translation elongation factor eEF2 is a novel tumor-associated antigen overexpressed in various types of cancers

Recent studies have shown that cancer immunotherapy could be a promising therapeutic approach for the treatment of cancer. In the present study, to identify novel tumor-associated antigens (TAAs), the proteins expressed in a panel of cancer cells were serologically screened by immunoblot analysis an...

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Veröffentlicht in:International journal of oncology 2014-05, Vol.44 (5), p.1461-1469
Hauptverfasser: OJI, YUSUKE, TATSUMI, NAOYA, FUKUDA, MARI, NAKATSUKA, SHIN-ICHI, AOYAGI, SAYAKA, HIRATA, ERIKA, NANCHI, ISAMU, FUJIKI, FUMIHIRO, NAKAJIMA, HIROKO, YAMAMOTO, YUMIKO, SHIBATA, SYOHEI, NAKAMURA, MICHIYO, HASEGAWA, KANA, TAKAGI, SAYAKA, FUKUDA, IKUYO, HOSHIKAWA, TOMOKO, MURAKAMI, YUI, MORI, MASAHIDE, INOUE, MASAYOSHI, NAKA, TETSUJI, TOMONAGA, TAKESHI, SHIMIZU, YOSHIFUMI, NAKAGAWA, MASASHI, HASEGAWA, JUNICHI, NEZU, RIICHIRO, INOHARA, HIDENORI, IZUMOTO, SHUICHI, NONOMURA, NORIO, YOSHIMINE, TOSHIKI, OKUMURA, MEINOSHIN, MORII, EIICHI, MAEDA, HAJIME, NISHIDA, SUMIYUKI, HOSEN, NAOKI, TSUBOI, AKIHIRO, OKA, YOSHIHIRO, SUGIYAMA, HARUO
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container_end_page 1469
container_issue 5
container_start_page 1461
container_title International journal of oncology
container_volume 44
creator OJI, YUSUKE
TATSUMI, NAOYA
FUKUDA, MARI
NAKATSUKA, SHIN-ICHI
AOYAGI, SAYAKA
HIRATA, ERIKA
NANCHI, ISAMU
FUJIKI, FUMIHIRO
NAKAJIMA, HIROKO
YAMAMOTO, YUMIKO
SHIBATA, SYOHEI
NAKAMURA, MICHIYO
HASEGAWA, KANA
TAKAGI, SAYAKA
FUKUDA, IKUYO
HOSHIKAWA, TOMOKO
MURAKAMI, YUI
MORI, MASAHIDE
INOUE, MASAYOSHI
NAKA, TETSUJI
TOMONAGA, TAKESHI
SHIMIZU, YOSHIFUMI
NAKAGAWA, MASASHI
HASEGAWA, JUNICHI
NEZU, RIICHIRO
INOHARA, HIDENORI
IZUMOTO, SHUICHI
NONOMURA, NORIO
YOSHIMINE, TOSHIKI
OKUMURA, MEINOSHIN
MORII, EIICHI
MAEDA, HAJIME
NISHIDA, SUMIYUKI
HOSEN, NAOKI
TSUBOI, AKIHIRO
OKA, YOSHIHIRO
SUGIYAMA, HARUO
description Recent studies have shown that cancer immunotherapy could be a promising therapeutic approach for the treatment of cancer. In the present study, to identify novel tumor-associated antigens (TAAs), the proteins expressed in a panel of cancer cells were serologically screened by immunoblot analysis and the eukaryotic elongation factor 2 (eEF2) was identified as an antigen that was recognized by IgG autoantibody in sera from a group of patients with head and neck squamous cell carcinoma (HNSCC) or colon cancer. Enzyme-linked immunosorbent assay showed that serum eEF2 IgG Ab levels were significantly higher in colorectal and gastric cancer patients compared to healthy individuals. Immunohistochemistry experiments showed that the eEF2 protein was overexpressed in the majority of lung, esophageal, pancreatic, breast and prostate cancers, HNSCC, glioblastoma multiforme and non-Hodgkin's lymphoma (NHL). Knockdown of eEF2 by short hairpin RNA (shRNA) significantly inhibited the growth in four eEF2-expressing cell lines, PC14 lung cancer, PCI6 pancreatic cancer, HT1080 fibrosarcoma and A172 glioblastoma cells, but not in eEF2-undetectable MCF7 cells. Furthermore, eEF2-derived 9-mer peptides, EF786 (eEF2 786-794 aa) and EF292 (eEF2 292-300 aa), elicited cytotoxic T lymphocyte (CTL) responses in peripheral blood mononuclear cells (PBMCs) from an HLA-A*24:02- and an HLA-A*02:01-positive healthy donor, respectively, in an HLA-A-restricted manner. These results indicated that the eEF2 gene is overexpressed in the majority of several types of cancers and plays an oncogenic role in cancer cell growth. Moreover, the eEF2 gene product is immunogenic and a promising target molecule of cancer immunotherapy for several types of cancers.
doi_str_mv 10.3892/ijo.2014.2318
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In the present study, to identify novel tumor-associated antigens (TAAs), the proteins expressed in a panel of cancer cells were serologically screened by immunoblot analysis and the eukaryotic elongation factor 2 (eEF2) was identified as an antigen that was recognized by IgG autoantibody in sera from a group of patients with head and neck squamous cell carcinoma (HNSCC) or colon cancer. Enzyme-linked immunosorbent assay showed that serum eEF2 IgG Ab levels were significantly higher in colorectal and gastric cancer patients compared to healthy individuals. Immunohistochemistry experiments showed that the eEF2 protein was overexpressed in the majority of lung, esophageal, pancreatic, breast and prostate cancers, HNSCC, glioblastoma multiforme and non-Hodgkin's lymphoma (NHL). Knockdown of eEF2 by short hairpin RNA (shRNA) significantly inhibited the growth in four eEF2-expressing cell lines, PC14 lung cancer, PCI6 pancreatic cancer, HT1080 fibrosarcoma and A172 glioblastoma cells, but not in eEF2-undetectable MCF7 cells. Furthermore, eEF2-derived 9-mer peptides, EF786 (eEF2 786-794 aa) and EF292 (eEF2 292-300 aa), elicited cytotoxic T lymphocyte (CTL) responses in peripheral blood mononuclear cells (PBMCs) from an HLA-A*24:02- and an HLA-A*02:01-positive healthy donor, respectively, in an HLA-A-restricted manner. These results indicated that the eEF2 gene is overexpressed in the majority of several types of cancers and plays an oncogenic role in cancer cell growth. Moreover, the eEF2 gene product is immunogenic and a promising target molecule of cancer immunotherapy for several types of cancers.</description><identifier>ISSN: 1019-6439</identifier><identifier>EISSN: 1791-2423</identifier><identifier>DOI: 10.3892/ijo.2014.2318</identifier><identifier>PMID: 24589652</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Analysis ; Antigens ; Antigens, Neoplasm - genetics ; Antigens, Neoplasm - metabolism ; autoantibody ; Breast cancer ; Cancer ; cancer immunotherapy ; Cancer therapies ; Cell cycle ; Cell growth ; Cell Line, Tumor ; cytotoxic T lymphocyte ; Elongation Factor 2 Kinase - genetics ; Elongation Factor 2 Kinase - metabolism ; Esophagus ; eukaryotic elongation factor 2 ; Gastric cancer ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Genetic aspects ; Health aspects ; Humans ; Immunoglobulin G - immunology ; Immunoglobulins ; Immunotherapy ; Leukemia ; Lung cancer ; Lymphoma ; Mass spectrometry ; MCF-7 Cells ; Neoplasms - genetics ; Neoplasms - immunology ; Neoplasms - pathology ; Oncology, Experimental ; Pancreatic cancer ; Physiological aspects ; Prostate ; Proteins ; Scientific imaging ; Sequence Analysis, DNA ; T-Lymphocytes, Cytotoxic - immunology ; tumor associated antigen</subject><ispartof>International journal of oncology, 2014-05, Vol.44 (5), p.1461-1469</ispartof><rights>Copyright © 2014, Spandidos Publications</rights><rights>COPYRIGHT 2014 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2014</rights><rights>Copyright © 2014, Spandidos Publications 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c611t-2dd678865c964a15873c77c5eb48e8778eafa2bd03146087700aa50c07fa789d3</citedby><cites>FETCH-LOGICAL-c611t-2dd678865c964a15873c77c5eb48e8778eafa2bd03146087700aa50c07fa789d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,5571,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24589652$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>OJI, YUSUKE</creatorcontrib><creatorcontrib>TATSUMI, NAOYA</creatorcontrib><creatorcontrib>FUKUDA, MARI</creatorcontrib><creatorcontrib>NAKATSUKA, SHIN-ICHI</creatorcontrib><creatorcontrib>AOYAGI, SAYAKA</creatorcontrib><creatorcontrib>HIRATA, ERIKA</creatorcontrib><creatorcontrib>NANCHI, ISAMU</creatorcontrib><creatorcontrib>FUJIKI, FUMIHIRO</creatorcontrib><creatorcontrib>NAKAJIMA, HIROKO</creatorcontrib><creatorcontrib>YAMAMOTO, YUMIKO</creatorcontrib><creatorcontrib>SHIBATA, SYOHEI</creatorcontrib><creatorcontrib>NAKAMURA, MICHIYO</creatorcontrib><creatorcontrib>HASEGAWA, KANA</creatorcontrib><creatorcontrib>TAKAGI, SAYAKA</creatorcontrib><creatorcontrib>FUKUDA, IKUYO</creatorcontrib><creatorcontrib>HOSHIKAWA, TOMOKO</creatorcontrib><creatorcontrib>MURAKAMI, YUI</creatorcontrib><creatorcontrib>MORI, MASAHIDE</creatorcontrib><creatorcontrib>INOUE, MASAYOSHI</creatorcontrib><creatorcontrib>NAKA, TETSUJI</creatorcontrib><creatorcontrib>TOMONAGA, TAKESHI</creatorcontrib><creatorcontrib>SHIMIZU, YOSHIFUMI</creatorcontrib><creatorcontrib>NAKAGAWA, MASASHI</creatorcontrib><creatorcontrib>HASEGAWA, JUNICHI</creatorcontrib><creatorcontrib>NEZU, RIICHIRO</creatorcontrib><creatorcontrib>INOHARA, HIDENORI</creatorcontrib><creatorcontrib>IZUMOTO, SHUICHI</creatorcontrib><creatorcontrib>NONOMURA, NORIO</creatorcontrib><creatorcontrib>YOSHIMINE, TOSHIKI</creatorcontrib><creatorcontrib>OKUMURA, MEINOSHIN</creatorcontrib><creatorcontrib>MORII, EIICHI</creatorcontrib><creatorcontrib>MAEDA, HAJIME</creatorcontrib><creatorcontrib>NISHIDA, SUMIYUKI</creatorcontrib><creatorcontrib>HOSEN, NAOKI</creatorcontrib><creatorcontrib>TSUBOI, AKIHIRO</creatorcontrib><creatorcontrib>OKA, YOSHIHIRO</creatorcontrib><creatorcontrib>SUGIYAMA, HARUO</creatorcontrib><title>The translation elongation factor eEF2 is a novel tumor-associated antigen overexpressed in various types of cancers</title><title>International journal of oncology</title><addtitle>Int J Oncol</addtitle><description>Recent studies have shown that cancer immunotherapy could be a promising therapeutic approach for the treatment of cancer. In the present study, to identify novel tumor-associated antigens (TAAs), the proteins expressed in a panel of cancer cells were serologically screened by immunoblot analysis and the eukaryotic elongation factor 2 (eEF2) was identified as an antigen that was recognized by IgG autoantibody in sera from a group of patients with head and neck squamous cell carcinoma (HNSCC) or colon cancer. Enzyme-linked immunosorbent assay showed that serum eEF2 IgG Ab levels were significantly higher in colorectal and gastric cancer patients compared to healthy individuals. Immunohistochemistry experiments showed that the eEF2 protein was overexpressed in the majority of lung, esophageal, pancreatic, breast and prostate cancers, HNSCC, glioblastoma multiforme and non-Hodgkin's lymphoma (NHL). Knockdown of eEF2 by short hairpin RNA (shRNA) significantly inhibited the growth in four eEF2-expressing cell lines, PC14 lung cancer, PCI6 pancreatic cancer, HT1080 fibrosarcoma and A172 glioblastoma cells, but not in eEF2-undetectable MCF7 cells. Furthermore, eEF2-derived 9-mer peptides, EF786 (eEF2 786-794 aa) and EF292 (eEF2 292-300 aa), elicited cytotoxic T lymphocyte (CTL) responses in peripheral blood mononuclear cells (PBMCs) from an HLA-A*24:02- and an HLA-A*02:01-positive healthy donor, respectively, in an HLA-A-restricted manner. These results indicated that the eEF2 gene is overexpressed in the majority of several types of cancers and plays an oncogenic role in cancer cell growth. Moreover, the eEF2 gene product is immunogenic and a promising target molecule of cancer immunotherapy for several types of cancers.</description><subject>Analysis</subject><subject>Antigens</subject><subject>Antigens, Neoplasm - genetics</subject><subject>Antigens, Neoplasm - metabolism</subject><subject>autoantibody</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>cancer immunotherapy</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>cytotoxic T lymphocyte</subject><subject>Elongation Factor 2 Kinase - genetics</subject><subject>Elongation Factor 2 Kinase - metabolism</subject><subject>Esophagus</subject><subject>eukaryotic elongation factor 2</subject><subject>Gastric cancer</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Knockdown Techniques</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunoglobulins</subject><subject>Immunotherapy</subject><subject>Leukemia</subject><subject>Lung cancer</subject><subject>Lymphoma</subject><subject>Mass spectrometry</subject><subject>MCF-7 Cells</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - immunology</subject><subject>Neoplasms - pathology</subject><subject>Oncology, Experimental</subject><subject>Pancreatic cancer</subject><subject>Physiological aspects</subject><subject>Prostate</subject><subject>Proteins</subject><subject>Scientific imaging</subject><subject>Sequence Analysis, DNA</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>tumor associated antigen</subject><issn>1019-6439</issn><issn>1791-2423</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptkk1rGzEQhpfS0ny0x16LoNCe1tXXrrSXQghJWgj0kp7FWDtry-xKrqQ1zb-vjFNjQ9FBw8wzL5rRW1UfGF0I3fGvbhMWnDK54ILpV9UlUx2rueTidYkp6-pWiu6iukppQylvGsreVhdcNrprG35Z5ac1khzBpxGyC57gGPzqEA5gc4gE7-45cYkA8WGHI8nzFGINKQXrIGNPwGe3Qk9KNeKfbcSUStZ5soPowpxIft5iImEgFrzFmN5VbwYYE75_ua-rX_d3T7ff68efDz9ubx5r2zKWa973rdK6bWzXSmCNVsIqZRtcSo1aKY0wAF_2VDDZ0pKgFKChlqoBlO56cV19O-hu5-WEvUVfJh3NNroJ4rMJ4Mx5xbu1WYWdkZSrjusi8OlFIIbfM6ZsNmGOvrzZsE5wwTuhT6gVjGicH0IRs5NL1txIVnbeKsoLtfgPVU6Pk7PB4-BK_qzh80nDGmHM6xTGef836RysD6CNIaWIw3FCRs3eJKaYxOxNYvYmKfzH07Uc6X-uKMCXA5C24HvXh3RkilItZU2buuycib9yScTL</recordid><startdate>20140501</startdate><enddate>20140501</enddate><creator>OJI, YUSUKE</creator><creator>TATSUMI, NAOYA</creator><creator>FUKUDA, MARI</creator><creator>NAKATSUKA, SHIN-ICHI</creator><creator>AOYAGI, SAYAKA</creator><creator>HIRATA, ERIKA</creator><creator>NANCHI, ISAMU</creator><creator>FUJIKI, FUMIHIRO</creator><creator>NAKAJIMA, HIROKO</creator><creator>YAMAMOTO, YUMIKO</creator><creator>SHIBATA, SYOHEI</creator><creator>NAKAMURA, MICHIYO</creator><creator>HASEGAWA, KANA</creator><creator>TAKAGI, SAYAKA</creator><creator>FUKUDA, IKUYO</creator><creator>HOSHIKAWA, TOMOKO</creator><creator>MURAKAMI, YUI</creator><creator>MORI, MASAHIDE</creator><creator>INOUE, MASAYOSHI</creator><creator>NAKA, TETSUJI</creator><creator>TOMONAGA, TAKESHI</creator><creator>SHIMIZU, YOSHIFUMI</creator><creator>NAKAGAWA, MASASHI</creator><creator>HASEGAWA, JUNICHI</creator><creator>NEZU, RIICHIRO</creator><creator>INOHARA, HIDENORI</creator><creator>IZUMOTO, SHUICHI</creator><creator>NONOMURA, NORIO</creator><creator>YOSHIMINE, TOSHIKI</creator><creator>OKUMURA, MEINOSHIN</creator><creator>MORII, EIICHI</creator><creator>MAEDA, HAJIME</creator><creator>NISHIDA, SUMIYUKI</creator><creator>HOSEN, NAOKI</creator><creator>TSUBOI, AKIHIRO</creator><creator>OKA, YOSHIHIRO</creator><creator>SUGIYAMA, HARUO</creator><general>D.A. Spandidos</general><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20140501</creationdate><title>The translation elongation factor eEF2 is a novel tumor-associated antigen overexpressed in various types of cancers</title><author>OJI, YUSUKE ; TATSUMI, NAOYA ; FUKUDA, MARI ; NAKATSUKA, SHIN-ICHI ; AOYAGI, SAYAKA ; HIRATA, ERIKA ; NANCHI, ISAMU ; FUJIKI, FUMIHIRO ; NAKAJIMA, HIROKO ; YAMAMOTO, YUMIKO ; SHIBATA, SYOHEI ; NAKAMURA, MICHIYO ; HASEGAWA, KANA ; TAKAGI, SAYAKA ; FUKUDA, IKUYO ; HOSHIKAWA, TOMOKO ; MURAKAMI, YUI ; MORI, MASAHIDE ; INOUE, MASAYOSHI ; NAKA, TETSUJI ; TOMONAGA, TAKESHI ; SHIMIZU, YOSHIFUMI ; NAKAGAWA, MASASHI ; HASEGAWA, JUNICHI ; NEZU, RIICHIRO ; INOHARA, HIDENORI ; IZUMOTO, SHUICHI ; NONOMURA, NORIO ; YOSHIMINE, TOSHIKI ; OKUMURA, MEINOSHIN ; MORII, EIICHI ; MAEDA, HAJIME ; NISHIDA, SUMIYUKI ; HOSEN, NAOKI ; TSUBOI, AKIHIRO ; OKA, YOSHIHIRO ; SUGIYAMA, HARUO</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c611t-2dd678865c964a15873c77c5eb48e8778eafa2bd03146087700aa50c07fa789d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Analysis</topic><topic>Antigens</topic><topic>Antigens, Neoplasm - genetics</topic><topic>Antigens, Neoplasm - metabolism</topic><topic>autoantibody</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>cancer immunotherapy</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>cytotoxic T lymphocyte</topic><topic>Elongation Factor 2 Kinase - genetics</topic><topic>Elongation Factor 2 Kinase - metabolism</topic><topic>Esophagus</topic><topic>eukaryotic elongation factor 2</topic><topic>Gastric cancer</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Knockdown Techniques</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Immunoglobulin G - immunology</topic><topic>Immunoglobulins</topic><topic>Immunotherapy</topic><topic>Leukemia</topic><topic>Lung cancer</topic><topic>Lymphoma</topic><topic>Mass spectrometry</topic><topic>MCF-7 Cells</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - immunology</topic><topic>Neoplasms - pathology</topic><topic>Oncology, Experimental</topic><topic>Pancreatic cancer</topic><topic>Physiological aspects</topic><topic>Prostate</topic><topic>Proteins</topic><topic>Scientific imaging</topic><topic>Sequence Analysis, DNA</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>tumor associated antigen</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>OJI, YUSUKE</creatorcontrib><creatorcontrib>TATSUMI, NAOYA</creatorcontrib><creatorcontrib>FUKUDA, MARI</creatorcontrib><creatorcontrib>NAKATSUKA, SHIN-ICHI</creatorcontrib><creatorcontrib>AOYAGI, SAYAKA</creatorcontrib><creatorcontrib>HIRATA, ERIKA</creatorcontrib><creatorcontrib>NANCHI, ISAMU</creatorcontrib><creatorcontrib>FUJIKI, FUMIHIRO</creatorcontrib><creatorcontrib>NAKAJIMA, HIROKO</creatorcontrib><creatorcontrib>YAMAMOTO, YUMIKO</creatorcontrib><creatorcontrib>SHIBATA, SYOHEI</creatorcontrib><creatorcontrib>NAKAMURA, MICHIYO</creatorcontrib><creatorcontrib>HASEGAWA, KANA</creatorcontrib><creatorcontrib>TAKAGI, SAYAKA</creatorcontrib><creatorcontrib>FUKUDA, IKUYO</creatorcontrib><creatorcontrib>HOSHIKAWA, TOMOKO</creatorcontrib><creatorcontrib>MURAKAMI, YUI</creatorcontrib><creatorcontrib>MORI, MASAHIDE</creatorcontrib><creatorcontrib>INOUE, MASAYOSHI</creatorcontrib><creatorcontrib>NAKA, TETSUJI</creatorcontrib><creatorcontrib>TOMONAGA, TAKESHI</creatorcontrib><creatorcontrib>SHIMIZU, YOSHIFUMI</creatorcontrib><creatorcontrib>NAKAGAWA, MASASHI</creatorcontrib><creatorcontrib>HASEGAWA, JUNICHI</creatorcontrib><creatorcontrib>NEZU, RIICHIRO</creatorcontrib><creatorcontrib>INOHARA, HIDENORI</creatorcontrib><creatorcontrib>IZUMOTO, SHUICHI</creatorcontrib><creatorcontrib>NONOMURA, NORIO</creatorcontrib><creatorcontrib>YOSHIMINE, TOSHIKI</creatorcontrib><creatorcontrib>OKUMURA, MEINOSHIN</creatorcontrib><creatorcontrib>MORII, EIICHI</creatorcontrib><creatorcontrib>MAEDA, HAJIME</creatorcontrib><creatorcontrib>NISHIDA, SUMIYUKI</creatorcontrib><creatorcontrib>HOSEN, NAOKI</creatorcontrib><creatorcontrib>TSUBOI, AKIHIRO</creatorcontrib><creatorcontrib>OKA, YOSHIHIRO</creatorcontrib><creatorcontrib>SUGIYAMA, HARUO</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing &amp; 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Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>OJI, YUSUKE</au><au>TATSUMI, NAOYA</au><au>FUKUDA, MARI</au><au>NAKATSUKA, SHIN-ICHI</au><au>AOYAGI, SAYAKA</au><au>HIRATA, ERIKA</au><au>NANCHI, ISAMU</au><au>FUJIKI, FUMIHIRO</au><au>NAKAJIMA, HIROKO</au><au>YAMAMOTO, YUMIKO</au><au>SHIBATA, SYOHEI</au><au>NAKAMURA, MICHIYO</au><au>HASEGAWA, KANA</au><au>TAKAGI, SAYAKA</au><au>FUKUDA, IKUYO</au><au>HOSHIKAWA, TOMOKO</au><au>MURAKAMI, YUI</au><au>MORI, MASAHIDE</au><au>INOUE, MASAYOSHI</au><au>NAKA, TETSUJI</au><au>TOMONAGA, TAKESHI</au><au>SHIMIZU, YOSHIFUMI</au><au>NAKAGAWA, MASASHI</au><au>HASEGAWA, JUNICHI</au><au>NEZU, RIICHIRO</au><au>INOHARA, HIDENORI</au><au>IZUMOTO, SHUICHI</au><au>NONOMURA, NORIO</au><au>YOSHIMINE, TOSHIKI</au><au>OKUMURA, MEINOSHIN</au><au>MORII, EIICHI</au><au>MAEDA, HAJIME</au><au>NISHIDA, SUMIYUKI</au><au>HOSEN, NAOKI</au><au>TSUBOI, AKIHIRO</au><au>OKA, YOSHIHIRO</au><au>SUGIYAMA, HARUO</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The translation elongation factor eEF2 is a novel tumor-associated antigen overexpressed in various types of cancers</atitle><jtitle>International journal of oncology</jtitle><addtitle>Int J Oncol</addtitle><date>2014-05-01</date><risdate>2014</risdate><volume>44</volume><issue>5</issue><spage>1461</spage><epage>1469</epage><pages>1461-1469</pages><issn>1019-6439</issn><eissn>1791-2423</eissn><abstract>Recent studies have shown that cancer immunotherapy could be a promising therapeutic approach for the treatment of cancer. In the present study, to identify novel tumor-associated antigens (TAAs), the proteins expressed in a panel of cancer cells were serologically screened by immunoblot analysis and the eukaryotic elongation factor 2 (eEF2) was identified as an antigen that was recognized by IgG autoantibody in sera from a group of patients with head and neck squamous cell carcinoma (HNSCC) or colon cancer. Enzyme-linked immunosorbent assay showed that serum eEF2 IgG Ab levels were significantly higher in colorectal and gastric cancer patients compared to healthy individuals. Immunohistochemistry experiments showed that the eEF2 protein was overexpressed in the majority of lung, esophageal, pancreatic, breast and prostate cancers, HNSCC, glioblastoma multiforme and non-Hodgkin's lymphoma (NHL). Knockdown of eEF2 by short hairpin RNA (shRNA) significantly inhibited the growth in four eEF2-expressing cell lines, PC14 lung cancer, PCI6 pancreatic cancer, HT1080 fibrosarcoma and A172 glioblastoma cells, but not in eEF2-undetectable MCF7 cells. Furthermore, eEF2-derived 9-mer peptides, EF786 (eEF2 786-794 aa) and EF292 (eEF2 292-300 aa), elicited cytotoxic T lymphocyte (CTL) responses in peripheral blood mononuclear cells (PBMCs) from an HLA-A*24:02- and an HLA-A*02:01-positive healthy donor, respectively, in an HLA-A-restricted manner. These results indicated that the eEF2 gene is overexpressed in the majority of several types of cancers and plays an oncogenic role in cancer cell growth. Moreover, the eEF2 gene product is immunogenic and a promising target molecule of cancer immunotherapy for several types of cancers.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>24589652</pmid><doi>10.3892/ijo.2014.2318</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects Analysis
Antigens
Antigens, Neoplasm - genetics
Antigens, Neoplasm - metabolism
autoantibody
Breast cancer
Cancer
cancer immunotherapy
Cancer therapies
Cell cycle
Cell growth
Cell Line, Tumor
cytotoxic T lymphocyte
Elongation Factor 2 Kinase - genetics
Elongation Factor 2 Kinase - metabolism
Esophagus
eukaryotic elongation factor 2
Gastric cancer
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Genetic aspects
Health aspects
Humans
Immunoglobulin G - immunology
Immunoglobulins
Immunotherapy
Leukemia
Lung cancer
Lymphoma
Mass spectrometry
MCF-7 Cells
Neoplasms - genetics
Neoplasms - immunology
Neoplasms - pathology
Oncology, Experimental
Pancreatic cancer
Physiological aspects
Prostate
Proteins
Scientific imaging
Sequence Analysis, DNA
T-Lymphocytes, Cytotoxic - immunology
tumor associated antigen
title The translation elongation factor eEF2 is a novel tumor-associated antigen overexpressed in various types of cancers
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