Pituitary tumour transforming gene (PTTG) induces genetic instability in thyroid cells
Cancer reflects the progressive accumulation of genetic alterations and subsequent genetic instability of cells. Cytogenetic studies have demonstrated the importance of aneuploidy in differentiated thyroid cancer development. The pituitary tumour transforming gene (PTTG), also known as securin, is a...
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| Veröffentlicht in: | Oncogene 2005-07, Vol.24 (30), p.4861-4866 |
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| description | Cancer reflects the progressive accumulation of genetic alterations and subsequent genetic instability of cells. Cytogenetic studies have demonstrated the importance of aneuploidy in differentiated thyroid cancer development. The pituitary tumour transforming gene (PTTG), also known as securin, is a mitotic checkpoint protein which inhibits sister chromatid separation during mitosis. PTTG is highly expressed in many cancers and overexpression of PTTG induces aneuploidy
in vitro
. Using fluorescent intersimple sequence repeat PCR (FISSR-PCR), we investigated the relationship between PTTG expression and the degree of genetic instability in normal and tumorous thyroid samples. The genomic instability index (GI index) was 6.7–72.7% higher in cancers than normal thyroid tissues. Follicular thyroid tumours exhibited greater genetic instability than papillary tumours (27.6% (
n
=9) versus 14.5% (
n
=10),
P
=0.03). We also demonstrated a strong relationship between PTTG expression and the degree of genetic instability in thyroid cancers (
R
2
=0.80,
P
=0.007). To further investigate PTTG's role in genetic instability, we transfected FTC133 thyroid follicular cells and observed increased genetic instability in cells overexpressing PTTG compared with vector-only-transfected controls (
n
=3, GI Index VO=29.7±5.2 versus PTTG=63.7±6.4,
P
=0.013). Further, we observed a dose response in genetic instability and PTTG expression (GI Index low dose (0.5
μ
g DNA/ six-well plate) PTTG=15.3%±1.7 versus high dose (3
μ
g DNA) PTTG=50.8%±3.3,
P
=0.006). Overall, we describe the first use of FISSR-PCR in human cancers, and demonstrate that PTTG expression correlates with genetic instability
in vivo
, and induces genetic instability
in vitro
. We conclude that PTTG may be an important gene in the mutator phenotype development in thyroid cancer. |
| doi_str_mv | 10.1038/sj.onc.1208659 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_68026680</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A189068492</galeid><sourcerecordid>A189068492</sourcerecordid><originalsourceid>FETCH-LOGICAL-c507t-33a10dc9b874667c8341e26d789d6e687bb8fe4f44cecd83096f6d56357fcc863</originalsourceid><addsrcrecordid>eNp1kc-L1DAUx4Mo7jh69aYURdFDZ_OjeUmOy6KrsOAeRq-hkyZjhjZdk_Qw_70Zp1CQXQLJy8vn_cj7IvSa4A3BTF6mw2YMZkMolsDVE7QijYCac9U8RSusOK4VZfQCvUjpgDEWCtPn6IJwqYqJV-jXnc-Tz208VnkaxilWObYhuTEOPuyrvQ22-nS33d58rnzoJmPTP1_2ptxTbne-9_lY7Cr_PsbRd5WxfZ9eomeu7ZN9NZ9r9PPrl-31t_r2x83366vb2nAscs1YS3Bn1E6KBkAYyRpiKXRCqg4sSLHbSWcb1zTGmk4yrMBBx4Fx4YyRwNbo4znvfRz_TDZlPfh06qANdpySBokplK2A7_8DD-WzofSmKTSEcU5AFOrdoxQVDDDlsKTat73VPrixjMyc6uorIhUG2ZSZr9HmAaqszg7ejME6X_wPBZg4phSt0_fRD0UYTbA-aa3TQRet9ax1CXg7NzvtBtst-CxuAT7MQJtM27sirPFp4UCB4pQU7vLMpfIU9jYuv3609JtzRGjzFO2Scn7_C5DOyWs</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>227360256</pqid></control><display><type>article</type><title>Pituitary tumour transforming gene (PTTG) induces genetic instability in thyroid cells</title><source>MEDLINE</source><source>Nature</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>SpringerLink Journals - AutoHoldings</source><creator>Kim, Dae ; Pemberton, Helen ; Stratford, Anna L ; Buelaert, Kristien ; Watkinson, John C ; Lopes, Victor ; Franklyn, Jayne A ; McCabe, Chris J</creator><creatorcontrib>Kim, Dae ; Pemberton, Helen ; Stratford, Anna L ; Buelaert, Kristien ; Watkinson, John C ; Lopes, Victor ; Franklyn, Jayne A ; McCabe, Chris J</creatorcontrib><description>Cancer reflects the progressive accumulation of genetic alterations and subsequent genetic instability of cells. Cytogenetic studies have demonstrated the importance of aneuploidy in differentiated thyroid cancer development. The pituitary tumour transforming gene (PTTG), also known as securin, is a mitotic checkpoint protein which inhibits sister chromatid separation during mitosis. PTTG is highly expressed in many cancers and overexpression of PTTG induces aneuploidy
in vitro
. Using fluorescent intersimple sequence repeat PCR (FISSR-PCR), we investigated the relationship between PTTG expression and the degree of genetic instability in normal and tumorous thyroid samples. The genomic instability index (GI index) was 6.7–72.7% higher in cancers than normal thyroid tissues. Follicular thyroid tumours exhibited greater genetic instability than papillary tumours (27.6% (
n
=9) versus 14.5% (
n
=10),
P
=0.03). We also demonstrated a strong relationship between PTTG expression and the degree of genetic instability in thyroid cancers (
R
2
=0.80,
P
=0.007). To further investigate PTTG's role in genetic instability, we transfected FTC133 thyroid follicular cells and observed increased genetic instability in cells overexpressing PTTG compared with vector-only-transfected controls (
n
=3, GI Index VO=29.7±5.2 versus PTTG=63.7±6.4,
P
=0.013). Further, we observed a dose response in genetic instability and PTTG expression (GI Index low dose (0.5
μ
g DNA/ six-well plate) PTTG=15.3%±1.7 versus high dose (3
μ
g DNA) PTTG=50.8%±3.3,
P
=0.006). Overall, we describe the first use of FISSR-PCR in human cancers, and demonstrate that PTTG expression correlates with genetic instability
in vivo
, and induces genetic instability
in vitro
. We conclude that PTTG may be an important gene in the mutator phenotype development in thyroid cancer.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1208659</identifier><identifier>PMID: 15897900</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Aneuploidy ; Apoptosis ; Biological and medical sciences ; Brain cancer ; Brain tumors ; Caspase 3 ; Caspase 7 ; Caspases - metabolism ; Cell Biology ; Cell Line ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Cytogenetics ; Deoxyribonucleic acid ; DNA ; DNA damage ; DNA repair ; Endocrinopathies ; Fundamental and applied biological sciences. Psychology ; Genomic Instability ; Human Genetics ; Humans ; Internal Medicine ; Kinases ; Malignant tumors ; Medical sciences ; Medicine ; Medicine & Public Health ; Mitosis ; Molecular and cellular biology ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; Non tumoral diseases. Target tissue resistance. Benign neoplasms ; Oncology ; Phenotypes ; Pituitary ; Pituitary gland ; Pituitary tumor-transforming proteins ; Polymerase chain reaction ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Securin ; short-report ; Thyrocytes ; Thyroid cancer ; Thyroid Gland - metabolism ; Thyroid Gland - pathology ; Thyroid Neoplasms - genetics ; Thyroid Neoplasms - pathology ; Thyroid. Thyroid axis (diseases) ; Tumors</subject><ispartof>Oncogene, 2005-07, Vol.24 (30), p.4861-4866</ispartof><rights>Springer Nature Limited 2005</rights><rights>2005 INIST-CNRS</rights><rights>COPYRIGHT 2005 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jul 14, 2005</rights><rights>Nature Publishing Group 2005.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c507t-33a10dc9b874667c8341e26d789d6e687bb8fe4f44cecd83096f6d56357fcc863</citedby><cites>FETCH-LOGICAL-c507t-33a10dc9b874667c8341e26d789d6e687bb8fe4f44cecd83096f6d56357fcc863</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.onc.1208659$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.onc.1208659$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,2727,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16969521$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15897900$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Dae</creatorcontrib><creatorcontrib>Pemberton, Helen</creatorcontrib><creatorcontrib>Stratford, Anna L</creatorcontrib><creatorcontrib>Buelaert, Kristien</creatorcontrib><creatorcontrib>Watkinson, John C</creatorcontrib><creatorcontrib>Lopes, Victor</creatorcontrib><creatorcontrib>Franklyn, Jayne A</creatorcontrib><creatorcontrib>McCabe, Chris J</creatorcontrib><title>Pituitary tumour transforming gene (PTTG) induces genetic instability in thyroid cells</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Cancer reflects the progressive accumulation of genetic alterations and subsequent genetic instability of cells. Cytogenetic studies have demonstrated the importance of aneuploidy in differentiated thyroid cancer development. The pituitary tumour transforming gene (PTTG), also known as securin, is a mitotic checkpoint protein which inhibits sister chromatid separation during mitosis. PTTG is highly expressed in many cancers and overexpression of PTTG induces aneuploidy
in vitro
. Using fluorescent intersimple sequence repeat PCR (FISSR-PCR), we investigated the relationship between PTTG expression and the degree of genetic instability in normal and tumorous thyroid samples. The genomic instability index (GI index) was 6.7–72.7% higher in cancers than normal thyroid tissues. Follicular thyroid tumours exhibited greater genetic instability than papillary tumours (27.6% (
n
=9) versus 14.5% (
n
=10),
P
=0.03). We also demonstrated a strong relationship between PTTG expression and the degree of genetic instability in thyroid cancers (
R
2
=0.80,
P
=0.007). To further investigate PTTG's role in genetic instability, we transfected FTC133 thyroid follicular cells and observed increased genetic instability in cells overexpressing PTTG compared with vector-only-transfected controls (
n
=3, GI Index VO=29.7±5.2 versus PTTG=63.7±6.4,
P
=0.013). Further, we observed a dose response in genetic instability and PTTG expression (GI Index low dose (0.5
μ
g DNA/ six-well plate) PTTG=15.3%±1.7 versus high dose (3
μ
g DNA) PTTG=50.8%±3.3,
P
=0.006). Overall, we describe the first use of FISSR-PCR in human cancers, and demonstrate that PTTG expression correlates with genetic instability
in vivo
, and induces genetic instability
in vitro
. We conclude that PTTG may be an important gene in the mutator phenotype development in thyroid cancer.</description><subject>Aneuploidy</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Brain cancer</subject><subject>Brain tumors</subject><subject>Caspase 3</subject><subject>Caspase 7</subject><subject>Caspases - metabolism</subject><subject>Cell Biology</subject><subject>Cell Line</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Cytogenetics</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA damage</subject><subject>DNA repair</subject><subject>Endocrinopathies</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genomic Instability</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Kinases</subject><subject>Malignant tumors</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mitosis</subject><subject>Molecular and cellular biology</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Non tumoral diseases. Target tissue resistance. Benign neoplasms</subject><subject>Oncology</subject><subject>Phenotypes</subject><subject>Pituitary</subject><subject>Pituitary gland</subject><subject>Pituitary tumor-transforming proteins</subject><subject>Polymerase chain reaction</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Securin</subject><subject>short-report</subject><subject>Thyrocytes</subject><subject>Thyroid cancer</subject><subject>Thyroid Gland - metabolism</subject><subject>Thyroid Gland - pathology</subject><subject>Thyroid Neoplasms - genetics</subject><subject>Thyroid Neoplasms - pathology</subject><subject>Thyroid. Thyroid axis (diseases)</subject><subject>Tumors</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kc-L1DAUx4Mo7jh69aYURdFDZ_OjeUmOy6KrsOAeRq-hkyZjhjZdk_Qw_70Zp1CQXQLJy8vn_cj7IvSa4A3BTF6mw2YMZkMolsDVE7QijYCac9U8RSusOK4VZfQCvUjpgDEWCtPn6IJwqYqJV-jXnc-Tz208VnkaxilWObYhuTEOPuyrvQ22-nS33d58rnzoJmPTP1_2ptxTbne-9_lY7Cr_PsbRd5WxfZ9eomeu7ZN9NZ9r9PPrl-31t_r2x83366vb2nAscs1YS3Bn1E6KBkAYyRpiKXRCqg4sSLHbSWcb1zTGmk4yrMBBx4Fx4YyRwNbo4znvfRz_TDZlPfh06qANdpySBokplK2A7_8DD-WzofSmKTSEcU5AFOrdoxQVDDDlsKTat73VPrixjMyc6uorIhUG2ZSZr9HmAaqszg7ejME6X_wPBZg4phSt0_fRD0UYTbA-aa3TQRet9ax1CXg7NzvtBtst-CxuAT7MQJtM27sirPFp4UCB4pQU7vLMpfIU9jYuv3609JtzRGjzFO2Scn7_C5DOyWs</recordid><startdate>20050714</startdate><enddate>20050714</enddate><creator>Kim, Dae</creator><creator>Pemberton, Helen</creator><creator>Stratford, Anna L</creator><creator>Buelaert, Kristien</creator><creator>Watkinson, John C</creator><creator>Lopes, Victor</creator><creator>Franklyn, Jayne A</creator><creator>McCabe, Chris J</creator><general>Nature Publishing Group UK</general><general>Nature Publishing</general><general>Nature Publishing Group</general><scope>IQODW</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>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20050714</creationdate><title>Pituitary tumour transforming gene (PTTG) induces genetic instability in thyroid cells</title><author>Kim, Dae ; Pemberton, Helen ; Stratford, Anna L ; Buelaert, Kristien ; Watkinson, John C ; Lopes, Victor ; Franklyn, Jayne A ; McCabe, Chris J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c507t-33a10dc9b874667c8341e26d789d6e687bb8fe4f44cecd83096f6d56357fcc863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Aneuploidy</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Brain cancer</topic><topic>Brain tumors</topic><topic>Caspase 3</topic><topic>Caspase 7</topic><topic>Caspases - metabolism</topic><topic>Cell Biology</topic><topic>Cell Line</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Cytogenetics</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA damage</topic><topic>DNA repair</topic><topic>Endocrinopathies</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genomic Instability</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Kinases</topic><topic>Malignant tumors</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mitosis</topic><topic>Molecular and cellular biology</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Non tumoral diseases. Target tissue resistance. Benign neoplasms</topic><topic>Oncology</topic><topic>Phenotypes</topic><topic>Pituitary</topic><topic>Pituitary gland</topic><topic>Pituitary tumor-transforming proteins</topic><topic>Polymerase chain reaction</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Securin</topic><topic>short-report</topic><topic>Thyrocytes</topic><topic>Thyroid cancer</topic><topic>Thyroid Gland - metabolism</topic><topic>Thyroid Gland - pathology</topic><topic>Thyroid Neoplasms - genetics</topic><topic>Thyroid Neoplasms - pathology</topic><topic>Thyroid. Thyroid axis (diseases)</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Dae</creatorcontrib><creatorcontrib>Pemberton, Helen</creatorcontrib><creatorcontrib>Stratford, Anna L</creatorcontrib><creatorcontrib>Buelaert, Kristien</creatorcontrib><creatorcontrib>Watkinson, John C</creatorcontrib><creatorcontrib>Lopes, Victor</creatorcontrib><creatorcontrib>Franklyn, Jayne A</creatorcontrib><creatorcontrib>McCabe, Chris J</creatorcontrib><collection>Pascal-Francis</collection><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>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</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>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Dae</au><au>Pemberton, Helen</au><au>Stratford, Anna L</au><au>Buelaert, Kristien</au><au>Watkinson, John C</au><au>Lopes, Victor</au><au>Franklyn, Jayne A</au><au>McCabe, Chris J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pituitary tumour transforming gene (PTTG) induces genetic instability in thyroid cells</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2005-07-14</date><risdate>2005</risdate><volume>24</volume><issue>30</issue><spage>4861</spage><epage>4866</epage><pages>4861-4866</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Cancer reflects the progressive accumulation of genetic alterations and subsequent genetic instability of cells. Cytogenetic studies have demonstrated the importance of aneuploidy in differentiated thyroid cancer development. The pituitary tumour transforming gene (PTTG), also known as securin, is a mitotic checkpoint protein which inhibits sister chromatid separation during mitosis. PTTG is highly expressed in many cancers and overexpression of PTTG induces aneuploidy
in vitro
. Using fluorescent intersimple sequence repeat PCR (FISSR-PCR), we investigated the relationship between PTTG expression and the degree of genetic instability in normal and tumorous thyroid samples. The genomic instability index (GI index) was 6.7–72.7% higher in cancers than normal thyroid tissues. Follicular thyroid tumours exhibited greater genetic instability than papillary tumours (27.6% (
n
=9) versus 14.5% (
n
=10),
P
=0.03). We also demonstrated a strong relationship between PTTG expression and the degree of genetic instability in thyroid cancers (
R
2
=0.80,
P
=0.007). To further investigate PTTG's role in genetic instability, we transfected FTC133 thyroid follicular cells and observed increased genetic instability in cells overexpressing PTTG compared with vector-only-transfected controls (
n
=3, GI Index VO=29.7±5.2 versus PTTG=63.7±6.4,
P
=0.013). Further, we observed a dose response in genetic instability and PTTG expression (GI Index low dose (0.5
μ
g DNA/ six-well plate) PTTG=15.3%±1.7 versus high dose (3
μ
g DNA) PTTG=50.8%±3.3,
P
=0.006). Overall, we describe the first use of FISSR-PCR in human cancers, and demonstrate that PTTG expression correlates with genetic instability
in vivo
, and induces genetic instability
in vitro
. We conclude that PTTG may be an important gene in the mutator phenotype development in thyroid cancer.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>15897900</pmid><doi>10.1038/sj.onc.1208659</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Oncogene, 2005-07, Vol.24 (30), p.4861-4866 |
| issn | 0950-9232 1476-5594 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68026680 |
| source | MEDLINE; Nature; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SpringerLink Journals - AutoHoldings |
| subjects | Aneuploidy Apoptosis Biological and medical sciences Brain cancer Brain tumors Caspase 3 Caspase 7 Caspases - metabolism Cell Biology Cell Line Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cytogenetics Deoxyribonucleic acid DNA DNA damage DNA repair Endocrinopathies Fundamental and applied biological sciences. Psychology Genomic Instability Human Genetics Humans Internal Medicine Kinases Malignant tumors Medical sciences Medicine Medicine & Public Health Mitosis Molecular and cellular biology Neoplasm Proteins - genetics Neoplasm Proteins - metabolism Non tumoral diseases. Target tissue resistance. Benign neoplasms Oncology Phenotypes Pituitary Pituitary gland Pituitary tumor-transforming proteins Polymerase chain reaction RNA, Messenger - genetics RNA, Messenger - metabolism Securin short-report Thyrocytes Thyroid cancer Thyroid Gland - metabolism Thyroid Gland - pathology Thyroid Neoplasms - genetics Thyroid Neoplasms - pathology Thyroid. Thyroid axis (diseases) Tumors |
| title | Pituitary tumour transforming gene (PTTG) induces genetic instability in thyroid cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T02%3A37%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pituitary%20tumour%20transforming%20gene%20(PTTG)%20induces%20genetic%20instability%20in%20thyroid%20cells&rft.jtitle=Oncogene&rft.au=Kim,%20Dae&rft.date=2005-07-14&rft.volume=24&rft.issue=30&rft.spage=4861&rft.epage=4866&rft.pages=4861-4866&rft.issn=0950-9232&rft.eissn=1476-5594&rft.coden=ONCNES&rft_id=info:doi/10.1038/sj.onc.1208659&rft_dat=%3Cgale_proqu%3EA189068492%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=227360256&rft_id=info:pmid/15897900&rft_galeid=A189068492&rfr_iscdi=true |