Epigenetic inactivation of protein kinase D1 in gastric cancer and its role in gastric cancer cell migration and invasion
Identifieur interne : 000E47 ( Istex/Corpus ); précédent : 000E46; suivant : 000E48Epigenetic inactivation of protein kinase D1 in gastric cancer and its role in gastric cancer cell migration and invasion
Auteurs : Mirang Kim ; Hay-Ran Jang ; Jeong-Hwan Kim ; Seung-Moo Noh ; Kyu-Sang Song ; June-Sik Cho ; Hyun-Yong Jeong ; Jim C. Norman ; Patrick T. Caswell ; Gyeong Hoon Kang ; Seon-Young Kim ; Hyang-Sook Yoo ; Yong Sung KimSource :
- Carcinogenesis [ 0143-3334 ] ; 2008-02-17.
Abstract
Protein kinase D (PKD) 1 influences cell migration by mediating both trans-Golgi vesicle fission and integrin recycling to the cell surface. Using restriction landmark genomic scanning methods, we found that the promoter region of PKD1 was aberrantly methylated in gastric cancer cell lines. Silencing of PKD1 expression was detected in 72.7% of gastric cancer cell lines examined, and the silencing was associated with CpG hypermethylation in the promoter region of PKD1. Treatment with 5-aza-2-deoxycytidine and trichostatin A partially reversed PKD1 methylation and restored gene expression in PKD1-silenced cell lines. Real-time reverse transcriptionpolymerase chain reaction analysis of 96 paired clinical primary gastric cancer samples revealed that 59% of the analyzed tumors had a >2-fold decrease in PKD1 expression compared with each normal-appearing tissue and that this downregulation of PKD1 expression was significantly correlated with increased methylation. We also observed a gradual increase in the level of promoter methylation of PKD1 in aging, normal-appearing mucosal tissues, suggesting that PKD1 methylation may be one of the earliest events that predispose an individual to gastric cancer. PKD1 expression was required for directional migration of gastric cancer cells. Furthermore, knock down of PKD1 by RNA interference promoted the invasiveness of cell lines that expressed PKD1 at relatively high levels. Based on these results, we propose that PKD1 is frequently silenced by epigenetic regulation, which plays a role in cell migration and metastasis in gastric cancer.
Url:
DOI: 10.1093/carcin/bgm291
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Caswell</name><affiliation><mods:affiliation>Integrin Cell Biology Laboratory, Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK</mods:affiliation></affiliation></author><author><name sortKey="Kang, Gyeong Hoon" sort="Kang, Gyeong Hoon" uniqKey="Kang G" first="Gyeong Hoon" last="Kang">Gyeong Hoon Kang</name><affiliation><mods:affiliation>Department of Pathology, Seoul National University College of Medicine, Seoul 110-744, Korea</mods:affiliation></affiliation></author><author><name sortKey="Kim, Seon Young" sort="Kim, Seon Young" uniqKey="Kim S" first="Seon-Young" last="Kim">Seon-Young Kim</name><affiliation><mods:affiliation>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</mods:affiliation></affiliation></author><author><name sortKey="Yoo, Hyang Sook" sort="Yoo, Hyang Sook" uniqKey="Yoo H" first="Hyang-Sook" last="Yoo">Hyang-Sook Yoo</name><affiliation><mods:affiliation>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</mods:affiliation></affiliation></author><author><name sortKey="Kim, Yong Sung" sort="Kim, Yong Sung" uniqKey="Kim Y" first="Yong Sung" last="Kim">Yong Sung Kim</name><affiliation><mods:affiliation>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Functional Genomics, University of Science and Technology, Daejeon 305-806, Korea</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: yongsung@kribb.re.kr</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Carcinogenesis</title><idno type="ISSN">0143-3334</idno><idno type="eISSN">1460-2180</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2008-02-17">2008-02-17</date><biblScope unit="volume">29</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="629">629</biblScope><biblScope unit="page" to="637">637</biblScope></imprint><idno type="ISSN">0143-3334</idno></series><idno type="istex">65E755DE405FA76CD9B924FFA71F56B0D3D89038</idno><idno type="DOI">10.1093/carcin/bgm291</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0143-3334</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Protein kinase D (PKD) 1 influences cell migration by mediating both trans-Golgi vesicle fission and integrin recycling to the cell surface. Using restriction landmark genomic scanning methods, we found that the promoter region of PKD1 was aberrantly methylated in gastric cancer cell lines. Silencing of PKD1 expression was detected in 72.7% of gastric cancer cell lines examined, and the silencing was associated with CpG hypermethylation in the promoter region of PKD1. Treatment with 5-aza-2-deoxycytidine and trichostatin A partially reversed PKD1 methylation and restored gene expression in PKD1-silenced cell lines. Real-time reverse transcriptionpolymerase chain reaction analysis of 96 paired clinical primary gastric cancer samples revealed that 59% of the analyzed tumors had a >2-fold decrease in PKD1 expression compared with each normal-appearing tissue and that this downregulation of PKD1 expression was significantly correlated with increased methylation. We also observed a gradual increase in the level of promoter methylation of PKD1 in aging, normal-appearing mucosal tissues, suggesting that PKD1 methylation may be one of the earliest events that predispose an individual to gastric cancer. PKD1 expression was required for directional migration of gastric cancer cells. Furthermore, knock down of PKD1 by RNA interference promoted the invasiveness of cell lines that expressed PKD1 at relatively high levels. Based on these results, we propose that PKD1 is frequently silenced by epigenetic regulation, which plays a role in cell migration and metastasis in gastric cancer.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Mirang Kim</name><affiliations><json:string>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</json:string><json:string>Department of Functional Genomics, University of Science and Technology, Daejeon 305-806, Korea</json:string></affiliations></json:item><json:item><name>Hay-Ran Jang</name><affiliations><json:string>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</json:string></affiliations></json:item><json:item><name>Jeong-Hwan Kim</name><affiliations><json:string>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</json:string></affiliations></json:item><json:item><name>Seung-Moo Noh</name><affiliations><json:string>Department of General Surgery</json:string></affiliations></json:item><json:item><name>Kyu-Sang Song</name><affiliations><json:string>Department of Pathology</json:string></affiliations></json:item><json:item><name>June-Sik Cho</name><affiliations><json:string>Department of Diagnostic Radiology and</json:string></affiliations></json:item><json:item><name>Hyun-Yong Jeong</name><affiliations><json:string>Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 301-747, Korea</json:string></affiliations></json:item><json:item><name>Jim C. Norman</name><affiliations><json:string>Integrin Cell Biology Laboratory, Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK</json:string></affiliations></json:item><json:item><name>Patrick T. Caswell</name><affiliations><json:string>Integrin Cell Biology Laboratory, Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK</json:string></affiliations></json:item><json:item><name>Gyeong Hoon Kang</name><affiliations><json:string>Department of Pathology, Seoul National University College of Medicine, Seoul 110-744, Korea</json:string></affiliations></json:item><json:item><name>Seon-Young Kim</name><affiliations><json:string>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</json:string></affiliations></json:item><json:item><name>Hyang-Sook Yoo</name><affiliations><json:string>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</json:string></affiliations></json:item><json:item><name>Yong Sung Kim</name><affiliations><json:string>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</json:string><json:string>Department of Functional Genomics, University of Science and Technology, Daejeon 305-806, Korea</json:string><json:string>E-mail: yongsung@kribb.re.kr</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>CARCINOGENESIS</value></json:item></subject><language><json:string>eng</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>Protein kinase D (PKD) 1 influences cell migration by mediating both trans-Golgi vesicle fission and integrin recycling to the cell surface. Using restriction landmark genomic scanning methods, we found that the promoter region of PKD1 was aberrantly methylated in gastric cancer cell lines. Silencing of PKD1 expression was detected in 72.7% of gastric cancer cell lines examined, and the silencing was associated with CpG hypermethylation in the promoter region of PKD1. Treatment with 5-aza-2-deoxycytidine and trichostatin A partially reversed PKD1 methylation and restored gene expression in PKD1-silenced cell lines. Real-time reverse transcriptionpolymerase chain reaction analysis of 96 paired clinical primary gastric cancer samples revealed that 59% of the analyzed tumors had a >2-fold decrease in PKD1 expression compared with each normal-appearing tissue and that this downregulation of PKD1 expression was significantly correlated with increased methylation. We also observed a gradual increase in the level of promoter methylation of PKD1 in aging, normal-appearing mucosal tissues, suggesting that PKD1 methylation may be one of the earliest events that predispose an individual to gastric cancer. PKD1 expression was required for directional migration of gastric cancer cells. Furthermore, knock down of PKD1 by RNA interference promoted the invasiveness of cell lines that expressed PKD1 at relatively high levels. 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Korea</affiliation><affiliation>Department of Functional Genomics, University of Science and Technology, Daejeon 305-806, Korea</affiliation></author><author xml:id="author-2"><persName><forename type="first">Hay-Ran</forename><surname>Jang</surname></persName><affiliation>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</affiliation></author><author xml:id="author-3"><persName><forename type="first">Jeong-Hwan</forename><surname>Kim</surname></persName><affiliation>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</affiliation></author><author xml:id="author-4"><persName><forename type="first">Seung-Moo</forename><surname>Noh</surname></persName><affiliation>Department of General Surgery</affiliation></author><author xml:id="author-5"><persName><forename type="first">Kyu-Sang</forename><surname>Song</surname></persName><affiliation>Department of Pathology</affiliation></author><author xml:id="author-6"><persName><forename type="first">June-Sik</forename><surname>Cho</surname></persName><affiliation>Department of Diagnostic Radiology and</affiliation></author><author xml:id="author-7"><persName><forename type="first">Hyun-Yong</forename><surname>Jeong</surname></persName><affiliation>Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 301-747, Korea</affiliation></author><author xml:id="author-8"><persName><forename type="first">Jim C.</forename><surname>Norman</surname></persName><affiliation>Integrin Cell Biology Laboratory, Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK</affiliation></author><author xml:id="author-9"><persName><forename type="first">Patrick T.</forename><surname>Caswell</surname></persName><affiliation>Integrin Cell Biology Laboratory, Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK</affiliation></author><author xml:id="author-10"><persName><forename type="first">Gyeong Hoon</forename><surname>Kang</surname></persName><affiliation>Department of Pathology, Seoul National University College of Medicine, Seoul 110-744, Korea</affiliation></author><author xml:id="author-11"><persName><forename type="first">Seon-Young</forename><surname>Kim</surname></persName><affiliation>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</affiliation></author><author xml:id="author-12"><persName><forename type="first">Hyang-Sook</forename><surname>Yoo</surname></persName><affiliation>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</affiliation></author><author xml:id="author-13" corresp="yes"><persName><forename type="first">Yong Sung</forename><surname>Kim</surname></persName><email>yongsung@kribb.re.kr</email><affiliation>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</affiliation><affiliation>Department of Functional Genomics, University of Science and Technology, Daejeon 305-806, Korea</affiliation></author></analytic><monogr><title level="j">Carcinogenesis</title><idno type="pISSN">0143-3334</idno><idno type="eISSN">1460-2180</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2008-02-17"></date><biblScope unit="volume">29</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="629">629</biblScope><biblScope unit="page" to="637">637</biblScope></imprint></monogr><idno type="istex">65E755DE405FA76CD9B924FFA71F56B0D3D89038</idno><idno type="DOI">10.1093/carcin/bgm291</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2008-02-17</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>Protein kinase D (PKD) 1 influences cell migration by mediating both trans-Golgi vesicle fission and integrin recycling to the cell surface. Using restriction landmark genomic scanning methods, we found that the promoter region of PKD1 was aberrantly methylated in gastric cancer cell lines. Silencing of PKD1 expression was detected in 72.7% of gastric cancer cell lines examined, and the silencing was associated with CpG hypermethylation in the promoter region of PKD1. Treatment with 5-aza-2-deoxycytidine and trichostatin A partially reversed PKD1 methylation and restored gene expression in PKD1-silenced cell lines. Real-time reverse transcriptionpolymerase chain reaction analysis of 96 paired clinical primary gastric cancer samples revealed that 59% of the analyzed tumors had a >2-fold decrease in PKD1 expression compared with each normal-appearing tissue and that this downregulation of PKD1 expression was significantly correlated with increased methylation. We also observed a gradual increase in the level of promoter methylation of PKD1 in aging, normal-appearing mucosal tissues, suggesting that PKD1 methylation may be one of the earliest events that predispose an individual to gastric cancer. PKD1 expression was required for directional migration of gastric cancer cells. Furthermore, knock down of PKD1 by RNA interference promoted the invasiveness of cell lines that expressed PKD1 at relatively high levels. Based on these results, we propose that PKD1 is frequently silenced by epigenetic regulation, which plays a role in cell migration and metastasis in gastric cancer.</p></abstract><textClass><keywords scheme="keyword"><list><item><term>CARCINOGENESIS</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2008-02-17">Created</change><change when="2008-02-17">Published</change><change xml:id="refBibs-istex" who="#ISTEX-API" when="2016-10-14">References added</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/65E755DE405FA76CD9B924FFA71F56B0D3D89038/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="hwp">carcin</journal-id><journal-id journal-id-type="publisher-id">carcin</journal-id><journal-title>Carcinogenesis</journal-title><issn pub-type="epub">1460-2180</issn><issn pub-type="ppub">0143-3334</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.1093/carcin/bgm291</article-id><article-categories><subj-group><subject>CARCINOGENESIS</subject></subj-group></article-categories><title-group><article-title>Epigenetic inactivation of protein kinase D1 in gastric cancer and its role in gastric cancer cell migration and invasion</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Mirang</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff8">8</xref></contrib><contrib contrib-type="author"><name><surname>Jang</surname><given-names>Hay-Ran</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Jeong-Hwan</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Noh</surname><given-names>Seung-Moo</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Song</surname><given-names>Kyu-Sang</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Cho</surname><given-names>June-Sik</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Jeong</surname><given-names>Hyun-Yong</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Norman</surname><given-names>Jim C.</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Caswell</surname><given-names>Patrick T.</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Kang</surname><given-names>Gyeong Hoon</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Seon-Young</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Yoo</surname><given-names>Hyang-Sook</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Kim</surname><given-names>Yong Sung</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff8">8</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</aff><aff id="aff2"><label>2</label>Department of General Surgery</aff><aff id="aff3"><label>3</label>Department of Pathology</aff><aff id="aff4"><label>4</label>Department of Diagnostic Radiology and</aff><aff id="aff5"><label>5</label>Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 301-747, Korea</aff><aff id="aff6"><label>6</label>Integrin Cell Biology Laboratory, Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK</aff><aff id="aff7"><label>7</label>Department of Pathology, Seoul National University College of Medicine, Seoul 110-744, Korea</aff><aff id="aff8"><label>8</label>Department of Functional Genomics, University of Science and Technology, Daejeon 305-806, Korea</aff><author-notes><corresp id="cor1"><label>*</label>To whom correspondence should be addressed. Tel: +82 42 879 8110; Fax: +82 42 879 8119; Email: <email>yongsung@kribb.re.kr</email></corresp></author-notes><pub-date pub-type="epub-ppub"><month>3</month><year>2008</year></pub-date><pub-date pub-type="epub"><day>17</day><month>2</month><year>2008</year></pub-date><volume>29</volume><issue>3</issue><fpage>629</fpage><lpage>637</lpage><history><date date-type="received"><day>3</day><month>9</month><year>2007</year></date><date date-type="rev-recd"><day>27</day><month>11</month><year>2007</year></date><date date-type="accepted"><day>27</day><month>11</month><year>2007</year></date></history><permissions><copyright-statement>© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org</copyright-statement><copyright-year>2008</copyright-year><license license-type="open-access"><p>The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org</p></license></permissions><abstract><p>Protein kinase D (PKD) 1 influences cell migration by mediating both <italic>trans</italic>-Golgi vesicle fission and integrin recycling to the cell surface. Using restriction landmark genomic scanning methods, we found that the promoter region of <italic>PKD1</italic> was aberrantly methylated in gastric cancer cell lines. Silencing of <italic>PKD1</italic> expression was detected in 72.7% of gastric cancer cell lines examined, and the silencing was associated with CpG hypermethylation in the promoter region of <italic>PKD1</italic>. Treatment with 5-aza-2′-deoxycytidine and trichostatin A partially reversed <italic>PKD1</italic> methylation and restored gene expression in <italic>PKD1</italic>-silenced cell lines. Real-time reverse transcription–polymerase chain reaction analysis of 96 paired clinical primary gastric cancer samples revealed that 59% of the analyzed tumors had a >2-fold decrease in <italic>PKD1</italic> expression compared with each normal-appearing tissue and that this downregulation of <italic>PKD1</italic> expression was significantly correlated with increased methylation. We also observed a gradual increase in the level of promoter methylation of <italic>PKD1</italic> in aging, normal-appearing mucosal tissues, suggesting that <italic>PKD1</italic> methylation may be one of the earliest events that predispose an individual to gastric cancer. PKD1 expression was required for directional migration of gastric cancer cells. Furthermore, knock down of PKD1 by RNA interference promoted the invasiveness of cell lines that expressed PKD1 at relatively high levels. Based on these results, we propose that <italic>PKD1</italic> is frequently silenced by epigenetic regulation, which plays a role in cell migration and metastasis in gastric cancer.</p></abstract></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Epigenetic inactivation of protein kinase D1 in gastric cancer and its role in gastric cancer cell migration and invasion</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Epigenetic inactivation of protein kinase D1 in gastric cancer and its role in gastric cancer cell migration and invasion</title></titleInfo><name type="personal"><namePart type="given">Mirang</namePart><namePart type="family">Kim</namePart><affiliation>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</affiliation><affiliation>Department of Functional Genomics, University of Science and Technology, Daejeon 305-806, Korea</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hay-Ran</namePart><namePart type="family">Jang</namePart><affiliation>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jeong-Hwan</namePart><namePart type="family">Kim</namePart><affiliation>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Seung-Moo</namePart><namePart type="family">Noh</namePart><affiliation>Department of General Surgery</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kyu-Sang</namePart><namePart type="family">Song</namePart><affiliation>Department of Pathology</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">June-Sik</namePart><namePart type="family">Cho</namePart><affiliation>Department of Diagnostic Radiology and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hyun-Yong</namePart><namePart type="family">Jeong</namePart><affiliation>Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon 301-747, Korea</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jim C.</namePart><namePart type="family">Norman</namePart><affiliation>Integrin Cell Biology Laboratory, Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Patrick T.</namePart><namePart type="family">Caswell</namePart><affiliation>Integrin Cell Biology Laboratory, Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gyeong Hoon</namePart><namePart type="family">Kang</namePart><affiliation>Department of Pathology, Seoul National University College of Medicine, Seoul 110-744, Korea</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Seon-Young</namePart><namePart type="family">Kim</namePart><affiliation>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hyang-Sook</namePart><namePart type="family">Yoo</namePart><affiliation>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">Yong Sung</namePart><namePart type="family">Kim</namePart><affiliation>Medical Genomics Research Center, KRIBB, Daejeon 305-806, Korea</affiliation><affiliation>Department of Functional Genomics, University of Science and Technology, Daejeon 305-806, Korea</affiliation><affiliation>E-mail: yongsung@kribb.re.kr</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><subject><topic>CARCINOGENESIS</topic></subject><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2008-02-17</dateIssued><dateCreated encoding="w3cdtf">2008-02-17</dateCreated><copyrightDate encoding="w3cdtf">2008</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" 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Using restriction landmark genomic scanning methods, we found that the promoter region of PKD1 was aberrantly methylated in gastric cancer cell lines. Silencing of PKD1 expression was detected in 72.7% of gastric cancer cell lines examined, and the silencing was associated with CpG hypermethylation in the promoter region of PKD1. Treatment with 5-aza-2-deoxycytidine and trichostatin A partially reversed PKD1 methylation and restored gene expression in PKD1-silenced cell lines. Real-time reverse transcriptionpolymerase chain reaction analysis of 96 paired clinical primary gastric cancer samples revealed that 59% of the analyzed tumors had a >2-fold decrease in PKD1 expression compared with each normal-appearing tissue and that this downregulation of PKD1 expression was significantly correlated with increased methylation. We also observed a gradual increase in the level of promoter methylation of PKD1 in aging, normal-appearing mucosal tissues, suggesting that PKD1 methylation may be one of the earliest events that predispose an individual to gastric cancer. PKD1 expression was required for directional migration of gastric cancer cells. Furthermore, knock down of PKD1 by RNA interference promoted the invasiveness of cell lines that expressed PKD1 at relatively high levels. 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