The human telomerase RNA gene (hTERC) is regulated during carcinogenesis but is not dependent on DNA methylation
Identifieur interne : 002416 ( Istex/Corpus ); précédent : 002415; suivant : 002417The human telomerase RNA gene (hTERC) is regulated during carcinogenesis but is not dependent on DNA methylation
Auteurs : Isabelle Guilleret ; Pu Yan ; Louis Guillou ; Richard Braunschweig ; Jean-Michel Coindre ; Jean BenhattarSource :
- Carcinogenesis [ 0143-3334 ] ; 2002-12.
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Abstract
Telomerase, the ribonucleoprotein complex involved in telomere maintenance, is composed of two main components: hTERT and hTERC. hTERT seems to be the rate-limiting factor for telomerase activity, although hTERC expression was also shown to correlate to a certain extent with telomerase reactivation. To determine whether the absence of hTERC expression could be the consequence of DNA methylation, we quantified hTERC RNA in 60 human samples (19 telomerase-negative normal tissues, nine telomerase-positive and 22 telomerase-negative tumor tissues, eight telomerase-positive and two telomerase-negative cell lines) using a quantitative dot blot on RT–PCR products. Most of the normal tissues did not express hTERC whereas, in telomerase-positive cell lines and in telomerase-positive tumor tissues, a strong up-regulation was observed, suggesting that hTERC transcription is up-regulated during tumorigenesis. The two telomerase-negative cell lines did not express hTERC. In a series of 22 telomerase-negative soft tissue sarcomas (STS), half did not express hTERC at all, or only weakly, whereas a wide range of expression was observed in the other half. As methylation might be involved in hTERC silencing, we examined the methylation pattern in all samples by direct sequencing and methylation-specific single stand conformation analysis after bisulfite modification. hTERC methylation was never observed, neither in normal nor in tumor tissues. Furthermore, there was no correlation between hTERC expression and proliferation, telomere length or hTERT expression in telomerase-negative STS. In contrast, three of eight telomerase-positive cell lines and the two telomerasenegative cell lines were found to be hypermethylated, suggesting that the methylation observed may occur during cell line establishment. In conclusion, this study shows that hTERC expression is indeed regulated during carcinogenesis, but this regulation is unlikely to depend on hTERC methylation, cell proliferation rate, telomere length or hTERT expression.
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DOI: 10.1093/carcin/23.12.2025
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">The human telomerase RNA gene (hTERC) is regulated during carcinogenesis but is not dependent on DNA methylation</title><author><name sortKey="Guilleret, Isabelle" sort="Guilleret, Isabelle" uniqKey="Guilleret I" first="Isabelle" last="Guilleret">Isabelle Guilleret</name><affiliation><mods:affiliation>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</mods:affiliation></affiliation></author><author><name sortKey="Yan, Pu" sort="Yan, Pu" uniqKey="Yan P" first="Pu" last="Yan">Pu Yan</name><affiliation><mods:affiliation>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</mods:affiliation></affiliation></author><author><name sortKey="Guillou, Louis" sort="Guillou, Louis" uniqKey="Guillou L" first="Louis" last="Guillou">Louis Guillou</name><affiliation><mods:affiliation>Institut de Pathologie, 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and</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:736B926E230D1B1111016B8BE1F8D91275AC2AD6</idno><date when="2002" year="2002">2002</date><idno type="doi">10.1093/carcin/23.12.2025</idno><idno type="url">https://api.istex.fr/document/736B926E230D1B1111016B8BE1F8D91275AC2AD6/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">002416</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">002416</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">The human telomerase RNA gene (hTERC) is regulated during carcinogenesis but is not dependent on DNA methylation</title><author><name sortKey="Guilleret, Isabelle" sort="Guilleret, Isabelle" uniqKey="Guilleret I" first="Isabelle" last="Guilleret">Isabelle Guilleret</name><affiliation><mods:affiliation>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</mods:affiliation></affiliation></author><author><name sortKey="Yan, Pu" sort="Yan, Pu" uniqKey="Yan P" first="Pu" last="Yan">Pu Yan</name><affiliation><mods:affiliation>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</mods:affiliation></affiliation></author><author><name sortKey="Guillou, Louis" sort="Guillou, Louis" uniqKey="Guillou L" first="Louis" last="Guillou">Louis Guillou</name><affiliation><mods:affiliation>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</mods:affiliation></affiliation></author><author><name sortKey="Braunschweig, Richard" sort="Braunschweig, Richard" uniqKey="Braunschweig R" first="Richard" last="Braunschweig">Richard Braunschweig</name><affiliation><mods:affiliation>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</mods:affiliation></affiliation></author><author><name sortKey="Coindre, Jean Michel" sort="Coindre, Jean Michel" uniqKey="Coindre J" first="Jean-Michel" last="Coindre">Jean-Michel Coindre</name><affiliation><mods:affiliation>Institut Bergonié, 33076 Bordeaux, France</mods:affiliation></affiliation></author><author><name sortKey="Benhattar, Jean" sort="Benhattar, Jean" uniqKey="Benhattar J" first="Jean" last="Benhattar">Jean Benhattar</name><affiliation><mods:affiliation>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Carcinogenesis</title><title level="j" type="abbrev">Carcinogenesis</title><idno type="ISSN">0143-3334</idno><idno type="eISSN">1460-2180</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2002-12">2002-12</date><biblScope unit="volume">23</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="2025">2025</biblScope><biblScope unit="page" to="2030">2030</biblScope></imprint><idno type="ISSN">0143-3334</idno></series><idno type="istex">736B926E230D1B1111016B8BE1F8D91275AC2AD6</idno><idno type="DOI">10.1093/carcin/23.12.2025</idno><idno type="PII">1460-2180</idno><idno type="local">0232025</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0143-3334</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>ALT, alternative lengthening of telomeres</term><term>MS-SSCA, methylation-specific single stand conformation analysis</term><term>STS, soft tissue sarcomas.</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Telomerase, the ribonucleoprotein complex involved in telomere maintenance, is composed of two main components: hTERT and hTERC. hTERT seems to be the rate-limiting factor for telomerase activity, although hTERC expression was also shown to correlate to a certain extent with telomerase reactivation. To determine whether the absence of hTERC expression could be the consequence of DNA methylation, we quantified hTERC RNA in 60 human samples (19 telomerase-negative normal tissues, nine telomerase-positive and 22 telomerase-negative tumor tissues, eight telomerase-positive and two telomerase-negative cell lines) using a quantitative dot blot on RT–PCR products. Most of the normal tissues did not express hTERC whereas, in telomerase-positive cell lines and in telomerase-positive tumor tissues, a strong up-regulation was observed, suggesting that hTERC transcription is up-regulated during tumorigenesis. The two telomerase-negative cell lines did not express hTERC. In a series of 22 telomerase-negative soft tissue sarcomas (STS), half did not express hTERC at all, or only weakly, whereas a wide range of expression was observed in the other half. As methylation might be involved in hTERC silencing, we examined the methylation pattern in all samples by direct sequencing and methylation-specific single stand conformation analysis after bisulfite modification. hTERC methylation was never observed, neither in normal nor in tumor tissues. Furthermore, there was no correlation between hTERC expression and proliferation, telomere length or hTERT expression in telomerase-negative STS. In contrast, three of eight telomerase-positive cell lines and the two telomerasenegative cell lines were found to be hypermethylated, suggesting that the methylation observed may occur during cell line establishment. In conclusion, this study shows that hTERC expression is indeed regulated during carcinogenesis, but this regulation is unlikely to depend on hTERC methylation, cell proliferation rate, telomere length or hTERT expression.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Isabelle Guilleret</name><affiliations><json:string>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</json:string></affiliations></json:item><json:item><name>Pu Yan</name><affiliations><json:string>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</json:string></affiliations></json:item><json:item><name>Louis Guillou</name><affiliations><json:string>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</json:string></affiliations></json:item><json:item><name>Richard Braunschweig</name><affiliations><json:string>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</json:string></affiliations></json:item><json:item><name>Jean-Michel Coindre</name><affiliations><json:string>Institut Bergonié, 33076 Bordeaux, France</json:string></affiliations></json:item><json:item><name>Jean Benhattar</name><affiliations><json:string>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>ALT, alternative lengthening of telomeres</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MS-SSCA, methylation-specific single stand conformation analysis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>STS, soft tissue sarcomas.</value></json:item></subject><language><json:string>eng</json:string></language><originalGenre><json:string>other</json:string></originalGenre><abstract>Telomerase, the ribonucleoprotein complex involved in telomere maintenance, is composed of two main components: hTERT and hTERC. hTERT seems to be the rate-limiting factor for telomerase activity, although hTERC expression was also shown to correlate to a certain extent with telomerase reactivation. To determine whether the absence of hTERC expression could be the consequence of DNA methylation, we quantified hTERC RNA in 60 human samples (19 telomerase-negative normal tissues, nine telomerase-positive and 22 telomerase-negative tumor tissues, eight telomerase-positive and two telomerase-negative cell lines) using a quantitative dot blot on RT–PCR products. Most of the normal tissues did not express hTERC whereas, in telomerase-positive cell lines and in telomerase-positive tumor tissues, a strong up-regulation was observed, suggesting that hTERC transcription is up-regulated during tumorigenesis. The two telomerase-negative cell lines did not express hTERC. In a series of 22 telomerase-negative soft tissue sarcomas (STS), half did not express hTERC at all, or only weakly, whereas a wide range of expression was observed in the other half. As methylation might be involved in hTERC silencing, we examined the methylation pattern in all samples by direct sequencing and methylation-specific single stand conformation analysis after bisulfite modification. hTERC methylation was never observed, neither in normal nor in tumor tissues. Furthermore, there was no correlation between hTERC expression and proliferation, telomere length or hTERT expression in telomerase-negative STS. In contrast, three of eight telomerase-positive cell lines and the two telomerasenegative cell lines were found to be hypermethylated, suggesting that the methylation observed may occur during cell line establishment. In conclusion, this study shows that hTERC expression is indeed regulated during carcinogenesis, but this regulation is unlikely to depend on hTERC methylation, cell proliferation rate, telomere length or hTERT expression.</abstract><qualityIndicators><score>9.787</score><pdfVersion>1.2</pdfVersion><pdfPageSize>612 x 792 pts (letter)</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>3</keywordCount><abstractCharCount>2036</abstractCharCount><pdfWordCount>4787</pdfWordCount><pdfCharCount>32386</pdfCharCount><pdfPageCount>6</pdfPageCount><abstractWordCount>283</abstractWordCount></qualityIndicators><title>The human telomerase RNA gene (hTERC) is regulated during carcinogenesis but is not dependent on DNA methylation</title><pii><json:string>1460-2180</json:string></pii><refBibs><json:item><host><volume>106</volume><pages><first>661</first></pages><author></author><title>Cell</title></host></json:item><json:item><host><volume>36</volume><pages><first>1619</first></pages><author></author><title>Exp. 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Cancer</title></host></json:item></refBibs><genre><json:string>other</json:string></genre><host><volume>23</volume><publisherId><json:string>carcin</json:string></publisherId><pages><last>2030</last><first>2025</first></pages><issn><json:string>0143-3334</json:string></issn><issue>12</issue><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1460-2180</json:string></eissn><title>Carcinogenesis</title></host><categories><wos><json:string>science</json:string><json:string>oncology</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>clinical medicine</json:string><json:string>oncology & carcinogenesis</json:string></scienceMetrix></categories><publicationDate>2002</publicationDate><copyrightDate>2002</copyrightDate><doi><json:string>10.1093/carcin/23.12.2025</json:string></doi><id>736B926E230D1B1111016B8BE1F8D91275AC2AD6</id><score>0.109686665</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/736B926E230D1B1111016B8BE1F8D91275AC2AD6/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/736B926E230D1B1111016B8BE1F8D91275AC2AD6/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/736B926E230D1B1111016B8BE1F8D91275AC2AD6/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">The human telomerase RNA gene (hTERC) is regulated during carcinogenesis but is not dependent on DNA methylation</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Oxford University Press</publisher><availability><p>© Oxford University Press</p></availability><date>2002</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">The human telomerase RNA gene (hTERC) is regulated during carcinogenesis but is not dependent on DNA methylation</title><author xml:id="author-1"><persName><forename type="first">Isabelle</forename><surname>Guilleret</surname></persName><affiliation>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</affiliation></author><author xml:id="author-2"><persName><forename type="first">Pu</forename><surname>Yan</surname></persName><affiliation>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</affiliation></author><author xml:id="author-3"><persName><forename type="first">Louis</forename><surname>Guillou</surname></persName><affiliation>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</affiliation></author><author xml:id="author-4"><persName><forename type="first">Richard</forename><surname>Braunschweig</surname></persName><affiliation>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</affiliation></author><author xml:id="author-5"><persName><forename type="first">Jean-Michel</forename><surname>Coindre</surname></persName><affiliation>Institut Bergonié, 33076 Bordeaux, France</affiliation></author><author xml:id="author-6"><persName><forename type="first">Jean</forename><surname>Benhattar</surname></persName><affiliation>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</affiliation></author></analytic><monogr><title level="j">Carcinogenesis</title><title level="j" type="abbrev">Carcinogenesis</title><idno type="pISSN">0143-3334</idno><idno type="eISSN">1460-2180</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2002-12"></date><biblScope unit="volume">23</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="2025">2025</biblScope><biblScope unit="page" to="2030">2030</biblScope></imprint></monogr><idno type="istex">736B926E230D1B1111016B8BE1F8D91275AC2AD6</idno><idno type="DOI">10.1093/carcin/23.12.2025</idno><idno type="PII">1460-2180</idno><idno type="local">0232025</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2002</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Telomerase, the ribonucleoprotein complex involved in telomere maintenance, is composed of two main components: hTERT and hTERC. hTERT seems to be the rate-limiting factor for telomerase activity, although hTERC expression was also shown to correlate to a certain extent with telomerase reactivation. To determine whether the absence of hTERC expression could be the consequence of DNA methylation, we quantified hTERC RNA in 60 human samples (19 telomerase-negative normal tissues, nine telomerase-positive and 22 telomerase-negative tumor tissues, eight telomerase-positive and two telomerase-negative cell lines) using a quantitative dot blot on RT–PCR products. Most of the normal tissues did not express hTERC whereas, in telomerase-positive cell lines and in telomerase-positive tumor tissues, a strong up-regulation was observed, suggesting that hTERC transcription is up-regulated during tumorigenesis. The two telomerase-negative cell lines did not express hTERC. In a series of 22 telomerase-negative soft tissue sarcomas (STS), half did not express hTERC at all, or only weakly, whereas a wide range of expression was observed in the other half. As methylation might be involved in hTERC silencing, we examined the methylation pattern in all samples by direct sequencing and methylation-specific single stand conformation analysis after bisulfite modification. hTERC methylation was never observed, neither in normal nor in tumor tissues. Furthermore, there was no correlation between hTERC expression and proliferation, telomere length or hTERT expression in telomerase-negative STS. In contrast, three of eight telomerase-positive cell lines and the two telomerasenegative cell lines were found to be hypermethylated, suggesting that the methylation observed may occur during cell line establishment. In conclusion, this study shows that hTERC expression is indeed regulated during carcinogenesis, but this regulation is unlikely to depend on hTERC methylation, cell proliferation rate, telomere length or hTERT expression.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>ABR</head><item><term>ALT, alternative lengthening of telomeres</term></item><item><term>MS-SSCA, methylation-specific single stand conformation analysis</term></item><item><term>STS, soft tissue sarcomas.</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2002-12">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/736B926E230D1B1111016B8BE1F8D91275AC2AD6/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="US-ASCII"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article xml:lang="en" article-type="other"><front><journal-meta><journal-id journal-id-type="hwp">carcin</journal-id><journal-id journal-id-type="nlm-ta">Carcinogenesis</journal-id><journal-id journal-id-type="publisher-id">carcin</journal-id><journal-title>Carcinogenesis</journal-title><abbrev-journal-title abbrev-type="publisher">Carcinogenesis</abbrev-journal-title><issn pub-type="ppub">0143-3334</issn><issn pub-type="epub">1460-2180</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.1093/carcin/23.12.2025</article-id><article-id pub-id-type="other">0232025</article-id><article-id pub-id-type="pii">1460-2180</article-id><article-categories><subj-group subj-group-type="heading"><subject>CANCER BIOLOGY</subject></subj-group></article-categories><title-group><article-title>The human telomerase RNA gene (<italic>hTERC</italic>) is regulated during carcinogenesis but is not dependent on DNA methylation</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Guilleret</surname><given-names>Isabelle</given-names></name><xref rid="AFF1">1</xref><xref rid="FN1">*</xref></contrib><contrib contrib-type="author"><name><surname>Yan</surname><given-names>Pu</given-names></name><xref rid="AFF1">1</xref><xref rid="FN1">*</xref></contrib><contrib contrib-type="author"><name><surname>Guillou</surname><given-names>Louis</given-names></name><xref rid="AFF1">1</xref></contrib><contrib contrib-type="author"><name><surname>Braunschweig</surname><given-names>Richard</given-names></name><xref rid="AFF1">1</xref></contrib><contrib contrib-type="author"><name><surname>Coindre</surname><given-names>Jean-Michel</given-names></name><xref rid="AFF2">2</xref></contrib><contrib contrib-type="author"><name><surname>Benhattar</surname><given-names>Jean</given-names></name><xref rid="AFF1">1</xref><xref rid="FN3">3</xref></contrib><aff id="AFF1"><label>1</label>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and </aff><aff id="AFF2"><label>2</label>Institut Bergonié, 33076 Bordeaux, France</aff></contrib-group><pub-date pub-type="ppub"><month>12</month><year>2002</year></pub-date><volume>23</volume><issue>12</issue><fpage>2025</fpage><lpage>2030</lpage><history><date date-type="accepted"><day>02</day><month>09</month><year>2002</year></date><date date-type="received"><day>24</day><month>06</month><year>2002</year></date><date date-type="rev-recd"><day>29</day><month>08</month><year>2002</year></date></history><permissions><copyright-statement>© Oxford University Press</copyright-statement><copyright-year>2002</copyright-year></permissions><abstract xml:lang="en"><p>Telomerase, the ribonucleoprotein complex involved in telomere maintenance, is composed of two main components: hTERT and hTERC. hTERT seems to be the rate-limiting factor for telomerase activity, although <italic>hTERC</italic> expression was also shown to correlate to a certain extent with telomerase reactivation. To determine whether the absence of <italic>hTERC</italic> expression could be the consequence of DNA methylation, we quantified <italic>hTERC</italic> RNA in 60 human samples (19 telomerase-negative normal tissues, nine telomerase-positive and 22 telomerase-negative tumor tissues, eight telomerase-positive and two telomerase-negative cell lines) using a quantitative dot blot on RT–PCR products. Most of the normal tissues did not express <italic>hTERC</italic> whereas, in telomerase-positive cell lines and in telomerase-positive tumor tissues, a strong up-regulation was observed, suggesting that <italic>hTERC</italic> transcription is up-regulated during tumorigenesis. The two telomerase-negative cell lines did not express <italic>hTERC</italic>. In a series of 22 telomerase-negative soft tissue sarcomas (STS), half did not express <italic>hTERC</italic> at all, or only weakly, whereas a wide range of expression was observed in the other half. As methylation might be involved in <italic>hTERC</italic> silencing, we examined the methylation pattern in all samples by direct sequencing and methylation-specific single stand conformation analysis after bisulfite modification. <italic>hTERC</italic> methylation was never observed, neither in normal nor in tumor tissues. Furthermore, there was no correlation between <italic>hTERC</italic> expression and proliferation, telomere length or <italic>hTERT</italic> expression in telomerase-negative STS. In contrast, three of eight telomerase-positive cell lines and the two telomerasenegative cell lines were found to be hypermethylated, suggesting that the methylation observed may occur during cell line establishment. In conclusion, this study shows that <italic>hTERC</italic> expression is indeed regulated during carcinogenesis, but this regulation is unlikely to depend on <italic>hTERC</italic> methylation, cell proliferation rate, telomere length or <italic>hTERT</italic> expression.</p></abstract><kwd-group kwd-group-type="ABR" xml:lang="en"><kwd>ALT, alternative lengthening of telomeres</kwd><kwd>MS-SSCA, methylation-specific single stand conformation analysis</kwd><kwd>STS, soft tissue sarcomas.</kwd></kwd-group><custom-meta-wrap><custom-meta><meta-name>hwp-legacy-fpage</meta-name><meta-value>2025</meta-value></custom-meta><custom-meta><meta-name>hwp-legacy-dochead</meta-name><meta-value>CANCER BIOLOGY</meta-value></custom-meta></custom-meta-wrap></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>The human telomerase RNA gene (hTERC) is regulated during carcinogenesis but is not dependent on DNA methylation</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>The human telomerase RNA gene (hTERC) is regulated during carcinogenesis but is not dependent on DNA methylation</title></titleInfo><name type="personal"><namePart type="given">Isabelle</namePart><namePart type="family">Guilleret</namePart><affiliation>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Pu</namePart><namePart type="family">Yan</namePart><affiliation>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Louis</namePart><namePart type="family">Guillou</namePart><affiliation>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Richard</namePart><namePart type="family">Braunschweig</namePart><affiliation>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean-Michel</namePart><namePart type="family">Coindre</namePart><affiliation>Institut Bergonié, 33076 Bordeaux, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean</namePart><namePart type="family">Benhattar</namePart><affiliation>Institut de Pathologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="other" displayLabel="other"></genre><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2002-12</dateIssued><copyrightDate encoding="w3cdtf">2002</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">Telomerase, the ribonucleoprotein complex involved in telomere maintenance, is composed of two main components: hTERT and hTERC. hTERT seems to be the rate-limiting factor for telomerase activity, although hTERC expression was also shown to correlate to a certain extent with telomerase reactivation. To determine whether the absence of hTERC expression could be the consequence of DNA methylation, we quantified hTERC RNA in 60 human samples (19 telomerase-negative normal tissues, nine telomerase-positive and 22 telomerase-negative tumor tissues, eight telomerase-positive and two telomerase-negative cell lines) using a quantitative dot blot on RT–PCR products. Most of the normal tissues did not express hTERC whereas, in telomerase-positive cell lines and in telomerase-positive tumor tissues, a strong up-regulation was observed, suggesting that hTERC transcription is up-regulated during tumorigenesis. The two telomerase-negative cell lines did not express hTERC. In a series of 22 telomerase-negative soft tissue sarcomas (STS), half did not express hTERC at all, or only weakly, whereas a wide range of expression was observed in the other half. As methylation might be involved in hTERC silencing, we examined the methylation pattern in all samples by direct sequencing and methylation-specific single stand conformation analysis after bisulfite modification. hTERC methylation was never observed, neither in normal nor in tumor tissues. Furthermore, there was no correlation between hTERC expression and proliferation, telomere length or hTERT expression in telomerase-negative STS. In contrast, three of eight telomerase-positive cell lines and the two telomerasenegative cell lines were found to be hypermethylated, suggesting that the methylation observed may occur during cell line establishment. In conclusion, this study shows that hTERC expression is indeed regulated during carcinogenesis, but this regulation is unlikely to depend on hTERC methylation, cell proliferation rate, telomere length or hTERT expression.</abstract><subject lang="en"><genre>ABR</genre><topic>ALT, alternative lengthening of telomeres</topic><topic>MS-SSCA, methylation-specific single stand conformation analysis</topic><topic>STS, soft tissue sarcomas.</topic></subject><relatedItem type="host"><titleInfo><title>Carcinogenesis</title></titleInfo><titleInfo type="abbreviated"><title>Carcinogenesis</title></titleInfo><genre type="journal">journal</genre><identifier type="ISSN">0143-3334</identifier><identifier type="eISSN">1460-2180</identifier><identifier type="PublisherID">carcin</identifier><identifier type="PublisherID-hwp">carcin</identifier><identifier type="PublisherID-nlm-ta">Carcinogenesis</identifier><part><date>2002</date><detail type="volume"><caption>vol.</caption><number>23</number></detail><detail type="issue"><caption>no.</caption><number>12</number></detail><extent unit="pages"><start>2025</start><end>2030</end></extent></part></relatedItem><identifier type="istex">736B926E230D1B1111016B8BE1F8D91275AC2AD6</identifier><identifier type="DOI">10.1093/carcin/23.12.2025</identifier><identifier type="PII">1460-2180</identifier><identifier type="local">0232025</identifier><accessCondition type="use and reproduction" contentType="copyright">© Oxford University Press</accessCondition><recordInfo><recordContentSource>OUP</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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