Antisense phosphorothioate oligonucleotides specifically down‐regulate cdc25B causing S‐phase delay and persistent antiproliferative effects
Cell cycle progression in mammalian cells is regulated by a family of cyclin‐dependent kinases (cdks) that are activated by a family of 3 cdc25 phosphatases: cdc25A, cdc25B and cdc25C. We examined the expression of mRNA and protein of all 3 cdc25s during the HeLa cell cycle, and found that cdc25B pr...
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| Veröffentlicht in: | International journal of cancer 1998-05, Vol.76 (5), p.720-728 |
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| container_title | International journal of cancer |
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| creator | Garner‐Hamrick, Peggy A. Fisher, Chris |
| description | Cell cycle progression in mammalian cells is regulated by a family of cyclin‐dependent kinases (cdks) that are activated by a family of 3 cdc25 phosphatases: cdc25A, cdc25B and cdc25C. We examined the expression of mRNA and protein of all 3 cdc25s during the HeLa cell cycle, and found that cdc25B protein has a unique and limited pattern of expression relative to other cdc25 homologs. Antisense oligonucleotides reduced cdc25B mRNA levels and dysregulated protein expression, while inhibiting S‐phase progression in synchronized HeLa cells. Scrambled control oligonucleotides had no effect. Antisense oligonucleotides transfected in early G2‐phase had no effect on cell cycle progression. A direct correlation between down‐regulation of cdc25B and inhibition of thymidine incorporation was found using several oligonucleotides. Our results suggest a role for cdc25B in S‐phase and demonstrate that inhibition of cdc25B has persistent antiproliferative effects. Int. J. Cancer 76:720–728, 1998.© 1998 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/(SICI)1097-0215(19980529)76:5<720::AID-IJC18>3.0.CO;2-7 |
| format | Article |
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We examined the expression of mRNA and protein of all 3 cdc25s during the HeLa cell cycle, and found that cdc25B protein has a unique and limited pattern of expression relative to other cdc25 homologs. Antisense oligonucleotides reduced cdc25B mRNA levels and dysregulated protein expression, while inhibiting S‐phase progression in synchronized HeLa cells. Scrambled control oligonucleotides had no effect. Antisense oligonucleotides transfected in early G2‐phase had no effect on cell cycle progression. A direct correlation between down‐regulation of cdc25B and inhibition of thymidine incorporation was found using several oligonucleotides. Our results suggest a role for cdc25B in S‐phase and demonstrate that inhibition of cdc25B has persistent antiproliferative effects. Int. J. Cancer 76:720–728, 1998.© 1998 Wiley‐Liss, Inc.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/(SICI)1097-0215(19980529)76:5<720::AID-IJC18>3.0.CO;2-7</identifier><identifier>PMID: 9610732</identifier><identifier>CODEN: IJCNAW</identifier><language>eng</language><publisher>New York: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Alternative Splicing ; Biological and medical sciences ; cdc25 Phosphatases ; Cell Cycle - physiology ; Cell Cycle Proteins - biosynthesis ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - physiology ; Cell cycle, cell proliferation ; Cell Division - drug effects ; Cell Division - physiology ; Cell physiology ; Down-Regulation - drug effects ; Fundamental and applied biological sciences. 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We examined the expression of mRNA and protein of all 3 cdc25s during the HeLa cell cycle, and found that cdc25B protein has a unique and limited pattern of expression relative to other cdc25 homologs. Antisense oligonucleotides reduced cdc25B mRNA levels and dysregulated protein expression, while inhibiting S‐phase progression in synchronized HeLa cells. Scrambled control oligonucleotides had no effect. Antisense oligonucleotides transfected in early G2‐phase had no effect on cell cycle progression. A direct correlation between down‐regulation of cdc25B and inhibition of thymidine incorporation was found using several oligonucleotides. Our results suggest a role for cdc25B in S‐phase and demonstrate that inhibition of cdc25B has persistent antiproliferative effects. Int. J. Cancer 76:720–728, 1998.© 1998 Wiley‐Liss, Inc.</description><subject>Alternative Splicing</subject><subject>Biological and medical sciences</subject><subject>cdc25 Phosphatases</subject><subject>Cell Cycle - physiology</subject><subject>Cell Cycle Proteins - biosynthesis</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - physiology</subject><subject>Cell cycle, cell proliferation</subject><subject>Cell Division - drug effects</subject><subject>Cell Division - physiology</subject><subject>Cell physiology</subject><subject>Down-Regulation - drug effects</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>HeLa Cells - cytology</subject><subject>HeLa Cells - drug effects</subject><subject>Humans</subject><subject>Isomerism</subject><subject>Molecular and cellular biology</subject><subject>Oligonucleotides, Antisense - pharmacology</subject><subject>Phosphoprotein Phosphatases - biosynthesis</subject><subject>Phosphoprotein Phosphatases - genetics</subject><subject>Phosphoprotein Phosphatases - physiology</subject><subject>RNA, Messenger - metabolism</subject><subject>S Phase - drug effects</subject><subject>S Phase - physiology</subject><subject>Sensitivity and Specificity</subject><subject>Thionucleotides - pharmacology</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcGO0zAURSMEGsrAJyBlgdDMIsV2ajsuCFTCAEUjdTEg2D05znNrlCYhThh1xyfMN_Il49DSDUiziKz4HV9f60TRG0qmlBD24uxqmS_PKVEyIYzyM6pURjhT51LM-SvJyHy-WL5Llp9ymr1Op2Sar16yRN6LJscz96NJSCKJpKl4GD3y_jshlHIyO4lOlKBEpmwS3Szq3nmsPcbtpvHh65p-4xrdY9xUbt3Ug6mw6V2JPvYtGmed0VW1i8vmuv7966bD9VCNtCkN429jowfv6nV8FWbtRofcEiu9i3Vdxi123vke6z789q7twg0WO927nxijtWh6_zh6YHXl8clhPY2-vL_4nH9MLlcflvniMjEzJrOkyEqjs4IKJowtM0W0sFZTjnJmURSGUaNKghyNKQoljdFUalFaQXnKdcbT0-j5Pje0-DGg72HrvMGq0jU2gwepFFFMZHeCVHDGZpQG8OseNF3jfYcW2s5tdbcDSmCUCjBKhVEQjILgr1SQAjgEqQBBKvyRCikQyFfAQIbkp4cKQ7HF8ph7sBjmzw5z7YMc2-naOH_EGOMkvDhg3_bYtatw90-7O8v9r9t-I70F6gnQlw</recordid><startdate>19980529</startdate><enddate>19980529</enddate><creator>Garner‐Hamrick, Peggy A.</creator><creator>Fisher, Chris</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</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>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19980529</creationdate><title>Antisense phosphorothioate oligonucleotides specifically down‐regulate cdc25B causing S‐phase delay and persistent antiproliferative effects</title><author>Garner‐Hamrick, Peggy A. ; Fisher, Chris</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4278-b8dca8b1626cfd890a6ffa15e74fe6bc21c9d0e5eccbb97cca17a6df61535a853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Alternative Splicing</topic><topic>Biological and medical sciences</topic><topic>cdc25 Phosphatases</topic><topic>Cell Cycle - physiology</topic><topic>Cell Cycle Proteins - biosynthesis</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - physiology</topic><topic>Cell cycle, cell proliferation</topic><topic>Cell Division - drug effects</topic><topic>Cell Division - physiology</topic><topic>Cell physiology</topic><topic>Down-Regulation - drug effects</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>HeLa Cells - cytology</topic><topic>HeLa Cells - drug effects</topic><topic>Humans</topic><topic>Isomerism</topic><topic>Molecular and cellular biology</topic><topic>Oligonucleotides, Antisense - pharmacology</topic><topic>Phosphoprotein Phosphatases - biosynthesis</topic><topic>Phosphoprotein Phosphatases - genetics</topic><topic>Phosphoprotein Phosphatases - physiology</topic><topic>RNA, Messenger - metabolism</topic><topic>S Phase - drug effects</topic><topic>S Phase - physiology</topic><topic>Sensitivity and Specificity</topic><topic>Thionucleotides - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Garner‐Hamrick, Peggy A.</creatorcontrib><creatorcontrib>Fisher, Chris</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>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Garner‐Hamrick, Peggy A.</au><au>Fisher, Chris</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antisense phosphorothioate oligonucleotides specifically down‐regulate cdc25B causing S‐phase delay and persistent antiproliferative effects</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>1998-05-29</date><risdate>1998</risdate><volume>76</volume><issue>5</issue><spage>720</spage><epage>728</epage><pages>720-728</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><coden>IJCNAW</coden><abstract>Cell cycle progression in mammalian cells is regulated by a family of cyclin‐dependent kinases (cdks) that are activated by a family of 3 cdc25 phosphatases: cdc25A, cdc25B and cdc25C. We examined the expression of mRNA and protein of all 3 cdc25s during the HeLa cell cycle, and found that cdc25B protein has a unique and limited pattern of expression relative to other cdc25 homologs. Antisense oligonucleotides reduced cdc25B mRNA levels and dysregulated protein expression, while inhibiting S‐phase progression in synchronized HeLa cells. Scrambled control oligonucleotides had no effect. Antisense oligonucleotides transfected in early G2‐phase had no effect on cell cycle progression. A direct correlation between down‐regulation of cdc25B and inhibition of thymidine incorporation was found using several oligonucleotides. Our results suggest a role for cdc25B in S‐phase and demonstrate that inhibition of cdc25B has persistent antiproliferative effects. Int. J. Cancer 76:720–728, 1998.© 1998 Wiley‐Liss, Inc.</abstract><cop>New York</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>9610732</pmid><doi>10.1002/(SICI)1097-0215(19980529)76:5<720::AID-IJC18>3.0.CO;2-7</doi><tpages>9</tpages></addata></record> |
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| ispartof | International journal of cancer, 1998-05, Vol.76 (5), p.720-728 |
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| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Wiley Online Library All Journals |
| subjects | Alternative Splicing Biological and medical sciences cdc25 Phosphatases Cell Cycle - physiology Cell Cycle Proteins - biosynthesis Cell Cycle Proteins - genetics Cell Cycle Proteins - physiology Cell cycle, cell proliferation Cell Division - drug effects Cell Division - physiology Cell physiology Down-Regulation - drug effects Fundamental and applied biological sciences. Psychology HeLa Cells - cytology HeLa Cells - drug effects Humans Isomerism Molecular and cellular biology Oligonucleotides, Antisense - pharmacology Phosphoprotein Phosphatases - biosynthesis Phosphoprotein Phosphatases - genetics Phosphoprotein Phosphatases - physiology RNA, Messenger - metabolism S Phase - drug effects S Phase - physiology Sensitivity and Specificity Thionucleotides - pharmacology |
| title | Antisense phosphorothioate oligonucleotides specifically down‐regulate cdc25B causing S‐phase delay and persistent antiproliferative effects |
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