Telomerase activity in HeLa cervical carcinoma cell line proliferation
Normal human somatic cells in culture have a limited dividing potential. This is due to DNA end replication problem, whereby telomeres shorten with each subsequent cell division. When a critical telomere length is reached cells enter senescence. To overcome this problem, immortal HeLa cell line expr...
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description | Normal human somatic cells in culture have a limited dividing potential. This is due to DNA end replication problem, whereby telomeres shorten with each subsequent cell division. When a critical telomere length is reached cells enter senescence. To overcome this problem, immortal HeLa cell line express telomerase, an enzyme that prevents telomere shortening. Although immortal, the existence of non-dividing cells that do not incorporate (3)H-thymidine over 24 h of growth has been well documented in this cell line. Using DiI labeling and high-speed cell sorting, we have separated and analyzed fractions of HeLa cells that divided vigorously as well as those that cease divisions over several days in culture. We also analyzed telomerase activity in separated fractions and surprisingly, found that the fraction of cells that divided 0-1 time over 6 days in culture have several times higher endogenous telomerase activity than the fastest dividing fraction. Additionally, the non-growing fraction regains an overall high labeling index and low SA-beta-Gal activity when subcultured again. This phenomenon should be considered if telomerase inhibition is to be used as an approach to cancer therapy. In this paper we also discuss possible molecular mechanisms that underlie the observed results. |
doi_str_mv | 10.1007/s10522-006-9043-9 |
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This is due to DNA end replication problem, whereby telomeres shorten with each subsequent cell division. When a critical telomere length is reached cells enter senescence. To overcome this problem, immortal HeLa cell line express telomerase, an enzyme that prevents telomere shortening. Although immortal, the existence of non-dividing cells that do not incorporate (3)H-thymidine over 24 h of growth has been well documented in this cell line. Using DiI labeling and high-speed cell sorting, we have separated and analyzed fractions of HeLa cells that divided vigorously as well as those that cease divisions over several days in culture. We also analyzed telomerase activity in separated fractions and surprisingly, found that the fraction of cells that divided 0-1 time over 6 days in culture have several times higher endogenous telomerase activity than the fastest dividing fraction. Additionally, the non-growing fraction regains an overall high labeling index and low SA-beta-Gal activity when subcultured again. This phenomenon should be considered if telomerase inhibition is to be used as an approach to cancer therapy. In this paper we also discuss possible molecular mechanisms that underlie the observed results.</description><identifier>ISSN: 1389-5729</identifier><identifier>EISSN: 1573-6768</identifier><identifier>DOI: 10.1007/s10522-006-9043-9</identifier><identifier>PMID: 16955216</identifier><language>eng</language><publisher>Dordrecht: Springer</publisher><subject>beta-Galactosidase - metabolism ; Biological and medical sciences ; Cancer therapies ; Carbocyanines ; Cell culture ; Cell division ; Cell Proliferation ; Cell Separation - methods ; Cellular Senescence ; Cervical carcinoma ; Cervix ; Development. Metamorphosis. Moult. Ageing ; DNA biosynthesis ; Enzymes ; Female ; Flow Cytometry ; Fluorescent Dyes ; Fundamental and applied biological sciences. Psychology ; Gene therapy ; HeLa Cells ; Humans ; Molecular modelling ; Phenotype ; Senescence ; Somatic cells ; Telomerase ; Telomerase - metabolism ; Telomeres ; Thymidine ; Time Factors ; Tritium ; Uterine Cervical Neoplasms - enzymology ; Uterine Cervical Neoplasms - pathology ; Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><ispartof>Biogerontology (Dordrecht), 2007-04, Vol.8 (2), p.163-172</ispartof><rights>2007 INIST-CNRS</rights><rights>Springer Science+Business Media B.V. 2006.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-5ca6bcf6375faa591a6ffdd71d60fe88406e0edaa0103d4d8921cfcf8605f2873</citedby><cites>FETCH-LOGICAL-c453t-5ca6bcf6375faa591a6ffdd71d60fe88406e0edaa0103d4d8921cfcf8605f2873</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18756940$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16955216$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>IVANKOVIC, Milena</creatorcontrib><creatorcontrib>CUKUSIC, Andrea</creatorcontrib><creatorcontrib>GOTIC, Ivana</creatorcontrib><creatorcontrib>SKROBOT, Nikolina</creatorcontrib><creatorcontrib>MATIJASIC, Mario</creatorcontrib><creatorcontrib>POLANCEC, Denis</creatorcontrib><creatorcontrib>RUBELJ, Ivica</creatorcontrib><title>Telomerase activity in HeLa cervical carcinoma cell line proliferation</title><title>Biogerontology (Dordrecht)</title><addtitle>Biogerontology</addtitle><description>Normal human somatic cells in culture have a limited dividing potential. This is due to DNA end replication problem, whereby telomeres shorten with each subsequent cell division. When a critical telomere length is reached cells enter senescence. To overcome this problem, immortal HeLa cell line express telomerase, an enzyme that prevents telomere shortening. Although immortal, the existence of non-dividing cells that do not incorporate (3)H-thymidine over 24 h of growth has been well documented in this cell line. Using DiI labeling and high-speed cell sorting, we have separated and analyzed fractions of HeLa cells that divided vigorously as well as those that cease divisions over several days in culture. We also analyzed telomerase activity in separated fractions and surprisingly, found that the fraction of cells that divided 0-1 time over 6 days in culture have several times higher endogenous telomerase activity than the fastest dividing fraction. Additionally, the non-growing fraction regains an overall high labeling index and low SA-beta-Gal activity when subcultured again. This phenomenon should be considered if telomerase inhibition is to be used as an approach to cancer therapy. In this paper we also discuss possible molecular mechanisms that underlie the observed results.</description><subject>beta-Galactosidase - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cancer therapies</subject><subject>Carbocyanines</subject><subject>Cell culture</subject><subject>Cell division</subject><subject>Cell Proliferation</subject><subject>Cell Separation - methods</subject><subject>Cellular Senescence</subject><subject>Cervical carcinoma</subject><subject>Cervix</subject><subject>Development. Metamorphosis. Moult. Ageing</subject><subject>DNA biosynthesis</subject><subject>Enzymes</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Fluorescent Dyes</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene therapy</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Molecular modelling</subject><subject>Phenotype</subject><subject>Senescence</subject><subject>Somatic cells</subject><subject>Telomerase</subject><subject>Telomerase - metabolism</subject><subject>Telomeres</subject><subject>Thymidine</subject><subject>Time Factors</subject><subject>Tritium</subject><subject>Uterine Cervical Neoplasms - enzymology</subject><subject>Uterine Cervical Neoplasms - pathology</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><issn>1389-5729</issn><issn>1573-6768</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkU1LAzEQhoMotlZ_gBdZBL2tTrKbr6MUa4WCl3oOaTaBlP2oyW6h_94sLRS8eMoQnnln5n0RusfwggH4a8RACckBWC6hLHJ5gaaY8iJnnInLVBdC5pQTOUE3MW4BMCOMXqMJZpJSgtkULda27hobdLSZNr3f-_6Q-TZb2pXOjA17b3SdGR2Mb7tm_KrrrPatzXahq71Lnb3v2lt05XQd7d3pnaHvxft6vsxXXx-f87dVbkpa9Dk1mm2MYwWnTmsqsWbOVRXHFQNnhSiBWbCV1oChqMpKSIKNM04woI4IXszQ81E3Tf8ZbOxV4-O4k25tN0TFgch0PP4XxJIlc7BM4OMfcNsNoU1HKJ4sIrzkIkH4CJnQxRisU7vgGx0OCoMao1DHKFSKQo1RqFH44SQ8bBpbnTtO3ifg6QTomEx2QbfGxzMnOGWyhOIX5zOQqA</recordid><startdate>20070401</startdate><enddate>20070401</enddate><creator>IVANKOVIC, Milena</creator><creator>CUKUSIC, Andrea</creator><creator>GOTIC, Ivana</creator><creator>SKROBOT, Nikolina</creator><creator>MATIJASIC, Mario</creator><creator>POLANCEC, Denis</creator><creator>RUBELJ, Ivica</creator><general>Springer</general><general>Springer Nature B.V</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>0-V</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88J</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ALSLI</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2R</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7TM</scope><scope>7X8</scope></search><sort><creationdate>20070401</creationdate><title>Telomerase activity in HeLa cervical carcinoma cell line proliferation</title><author>IVANKOVIC, Milena ; CUKUSIC, Andrea ; GOTIC, Ivana ; SKROBOT, Nikolina ; MATIJASIC, Mario ; POLANCEC, Denis ; RUBELJ, Ivica</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-5ca6bcf6375faa591a6ffdd71d60fe88406e0edaa0103d4d8921cfcf8605f2873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>beta-Galactosidase - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cancer therapies</topic><topic>Carbocyanines</topic><topic>Cell culture</topic><topic>Cell division</topic><topic>Cell Proliferation</topic><topic>Cell Separation - methods</topic><topic>Cellular Senescence</topic><topic>Cervical carcinoma</topic><topic>Cervix</topic><topic>Development. Metamorphosis. Moult. Ageing</topic><topic>DNA biosynthesis</topic><topic>Enzymes</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Fluorescent Dyes</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene therapy</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Molecular modelling</topic><topic>Phenotype</topic><topic>Senescence</topic><topic>Somatic cells</topic><topic>Telomerase</topic><topic>Telomerase - metabolism</topic><topic>Telomeres</topic><topic>Thymidine</topic><topic>Time Factors</topic><topic>Tritium</topic><topic>Uterine Cervical Neoplasms - enzymology</topic><topic>Uterine Cervical Neoplasms - pathology</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>IVANKOVIC, Milena</creatorcontrib><creatorcontrib>CUKUSIC, Andrea</creatorcontrib><creatorcontrib>GOTIC, Ivana</creatorcontrib><creatorcontrib>SKROBOT, Nikolina</creatorcontrib><creatorcontrib>MATIJASIC, Mario</creatorcontrib><creatorcontrib>POLANCEC, Denis</creatorcontrib><creatorcontrib>RUBELJ, Ivica</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 Social Sciences Premium Collection</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Social Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Social Science Premium Collection</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>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Social Science Database</collection><collection>Biological Science Database</collection><collection>Nursing & 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>ProQuest Central Basic</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biogerontology (Dordrecht)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>IVANKOVIC, Milena</au><au>CUKUSIC, Andrea</au><au>GOTIC, Ivana</au><au>SKROBOT, Nikolina</au><au>MATIJASIC, Mario</au><au>POLANCEC, Denis</au><au>RUBELJ, Ivica</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Telomerase activity in HeLa cervical carcinoma cell line proliferation</atitle><jtitle>Biogerontology (Dordrecht)</jtitle><addtitle>Biogerontology</addtitle><date>2007-04-01</date><risdate>2007</risdate><volume>8</volume><issue>2</issue><spage>163</spage><epage>172</epage><pages>163-172</pages><issn>1389-5729</issn><eissn>1573-6768</eissn><abstract>Normal human somatic cells in culture have a limited dividing potential. This is due to DNA end replication problem, whereby telomeres shorten with each subsequent cell division. When a critical telomere length is reached cells enter senescence. To overcome this problem, immortal HeLa cell line express telomerase, an enzyme that prevents telomere shortening. Although immortal, the existence of non-dividing cells that do not incorporate (3)H-thymidine over 24 h of growth has been well documented in this cell line. Using DiI labeling and high-speed cell sorting, we have separated and analyzed fractions of HeLa cells that divided vigorously as well as those that cease divisions over several days in culture. We also analyzed telomerase activity in separated fractions and surprisingly, found that the fraction of cells that divided 0-1 time over 6 days in culture have several times higher endogenous telomerase activity than the fastest dividing fraction. Additionally, the non-growing fraction regains an overall high labeling index and low SA-beta-Gal activity when subcultured again. This phenomenon should be considered if telomerase inhibition is to be used as an approach to cancer therapy. In this paper we also discuss possible molecular mechanisms that underlie the observed results.</abstract><cop>Dordrecht</cop><pub>Springer</pub><pmid>16955216</pmid><doi>10.1007/s10522-006-9043-9</doi><tpages>10</tpages></addata></record> |
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subjects | beta-Galactosidase - metabolism Biological and medical sciences Cancer therapies Carbocyanines Cell culture Cell division Cell Proliferation Cell Separation - methods Cellular Senescence Cervical carcinoma Cervix Development. Metamorphosis. Moult. Ageing DNA biosynthesis Enzymes Female Flow Cytometry Fluorescent Dyes Fundamental and applied biological sciences. Psychology Gene therapy HeLa Cells Humans Molecular modelling Phenotype Senescence Somatic cells Telomerase Telomerase - metabolism Telomeres Thymidine Time Factors Tritium Uterine Cervical Neoplasms - enzymology Uterine Cervical Neoplasms - pathology Vertebrates: anatomy and physiology, studies on body, several organs or systems |
title | Telomerase activity in HeLa cervical carcinoma cell line proliferation |
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