Human T-cell leukemia virus type I tax transformation is associated with increased uptake of oligodeoxynucleotides in vitro and in vivo
We have utilized antisense oligodeoxynucleotides (ODNs) to modulate transcriptional activation by the human T-cell leukemia virus type I (HTLV-I) tax gene, the major transcriptional regulator of this virus. 3'-Terminal phosphorothioate-modified antisense ODNs were shown to efficiently inhibit T...
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| Veröffentlicht in: | The Journal of biological chemistry 1992-12, Vol.267 (36), p.25881-25888 |
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| container_issue | 36 |
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| container_title | The Journal of biological chemistry |
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| creator | KITAJIMA, I SHINOHARA, T MINOR, T BIBBS, L BILAKOVICS, J NERENBERG, M |
| description | We have utilized antisense oligodeoxynucleotides (ODNs) to modulate transcriptional activation by the human T-cell leukemia
virus type I (HTLV-I) tax gene, the major transcriptional regulator of this virus. 3'-Terminal phosphorothioate-modified antisense
ODNs were shown to efficiently inhibit Tax protein expression both in vitro and in vivo. Terminal substitution did not affect
the affinity of ODNs for their target sequence but conferred a 9-fold increase in tax inhibition in vitro. When delivered
into mice by intraperitoneal injection, ODNs inhibited tax expression in established tumors by 90%. Unmanipulated tax-transformed
mouse fibroblasts, or HTLV-I-transformed human lymphocytes, showed at least 5-fold higher ODN binding and uptake over control
cells. Balb/3T3 cell binding was induced to similar levels by cellular activators. This suggests that constitutive activation
by tax transformation may increase susceptibility of HTLV-I-transformed cells to antisense therapy, providing a rationale
for the use of antisense ODN therapeutics in HTLV-I-associated diseases. |
| doi_str_mv | 10.1016/S0021-9258(18)35691-6 |
| format | Article |
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virus type I (HTLV-I) tax gene, the major transcriptional regulator of this virus. 3'-Terminal phosphorothioate-modified antisense
ODNs were shown to efficiently inhibit Tax protein expression both in vitro and in vivo. Terminal substitution did not affect
the affinity of ODNs for their target sequence but conferred a 9-fold increase in tax inhibition in vitro. When delivered
into mice by intraperitoneal injection, ODNs inhibited tax expression in established tumors by 90%. Unmanipulated tax-transformed
mouse fibroblasts, or HTLV-I-transformed human lymphocytes, showed at least 5-fold higher ODN binding and uptake over control
cells. Balb/3T3 cell binding was induced to similar levels by cellular activators. This suggests that constitutive activation
by tax transformation may increase susceptibility of HTLV-I-transformed cells to antisense therapy, providing a rationale
for the use of antisense ODN therapeutics in HTLV-I-associated diseases.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1016/S0021-9258(18)35691-6</identifier><identifier>PMID: 1281476</identifier><identifier>CODEN: JBCHA3</identifier><language>eng</language><publisher>Bethesda, MD: American Society for Biochemistry and Molecular Biology</publisher><subject>3T3 Cells ; Action of physical and chemical agents ; Animals ; Base Sequence ; Biological and medical sciences ; Biological Transport ; Blotting, Northern ; Cell Line ; Cell Transformation, Neoplastic ; Female ; Fundamental and applied biological sciences. Psychology ; Genes, pX - drug effects ; Human T-lymphotropic virus 1 - drug effects ; Human T-lymphotropic virus 1 - genetics ; Kinetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mice, Transgenic ; Microbiology ; Molecular Sequence Data ; Oligodeoxyribonucleotides - metabolism ; Oligodeoxyribonucleotides - pharmacology ; Oligonucleotides, Antisense - metabolism ; Oligonucleotides, Antisense - pharmacology ; Organ Specificity ; Repetitive Sequences, Nucleic Acid ; RNA - genetics ; RNA - isolation & purification ; Transcriptional Activation - drug effects ; Virology</subject><ispartof>The Journal of biological chemistry, 1992-12, Vol.267 (36), p.25881-25888</ispartof><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3556-bfb7e39b5d5ca53ea3d5ecd29c132a3d8cebe7a0326df24fd363df0d844d8b053</citedby><cites>FETCH-LOGICAL-c3556-bfb7e39b5d5ca53ea3d5ecd29c132a3d8cebe7a0326df24fd363df0d844d8b053</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4554833$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1281476$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KITAJIMA, I</creatorcontrib><creatorcontrib>SHINOHARA, T</creatorcontrib><creatorcontrib>MINOR, T</creatorcontrib><creatorcontrib>BIBBS, L</creatorcontrib><creatorcontrib>BILAKOVICS, J</creatorcontrib><creatorcontrib>NERENBERG, M</creatorcontrib><title>Human T-cell leukemia virus type I tax transformation is associated with increased uptake of oligodeoxynucleotides in vitro and in vivo</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>We have utilized antisense oligodeoxynucleotides (ODNs) to modulate transcriptional activation by the human T-cell leukemia
virus type I (HTLV-I) tax gene, the major transcriptional regulator of this virus. 3'-Terminal phosphorothioate-modified antisense
ODNs were shown to efficiently inhibit Tax protein expression both in vitro and in vivo. Terminal substitution did not affect
the affinity of ODNs for their target sequence but conferred a 9-fold increase in tax inhibition in vitro. When delivered
into mice by intraperitoneal injection, ODNs inhibited tax expression in established tumors by 90%. Unmanipulated tax-transformed
mouse fibroblasts, or HTLV-I-transformed human lymphocytes, showed at least 5-fold higher ODN binding and uptake over control
cells. Balb/3T3 cell binding was induced to similar levels by cellular activators. This suggests that constitutive activation
by tax transformation may increase susceptibility of HTLV-I-transformed cells to antisense therapy, providing a rationale
for the use of antisense ODN therapeutics in HTLV-I-associated diseases.</description><subject>3T3 Cells</subject><subject>Action of physical and chemical agents</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Biological Transport</subject><subject>Blotting, Northern</subject><subject>Cell Line</subject><subject>Cell Transformation, Neoplastic</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genes, pX - drug effects</subject><subject>Human T-lymphotropic virus 1 - drug effects</subject><subject>Human T-lymphotropic virus 1 - genetics</subject><subject>Kinetics</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred DBA</subject><subject>Mice, Transgenic</subject><subject>Microbiology</subject><subject>Molecular Sequence Data</subject><subject>Oligodeoxyribonucleotides - metabolism</subject><subject>Oligodeoxyribonucleotides - pharmacology</subject><subject>Oligonucleotides, Antisense - metabolism</subject><subject>Oligonucleotides, Antisense - pharmacology</subject><subject>Organ Specificity</subject><subject>Repetitive Sequences, Nucleic Acid</subject><subject>RNA - genetics</subject><subject>RNA - isolation & purification</subject><subject>Transcriptional Activation - drug effects</subject><subject>Virology</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkU1OHDEQhS2UiEyAIyB5EUXJoond_hn3MkIkICGxCJGys9x2mTF0tye2G5gT5NrxMCPwxnqqr6pU7yF0SskZJVR--0VIS5uuFeoLVV-ZkB1t5AFaUKJYwwT98w4tXpEP6GPO96Q-3tFDdEhbRflSLtC_y3k0E75tLAwDHmB-gDEY_BjSnHHZrAFf4WKecUlmyj6m0ZQQJxwyNjlHG0wBh59CWeEw2QQmVzmvi3kAHD2OQ7iLDuLzZprtALEEB7mSdX5JEZvJ7cRjPEbvvRkynOz_I_T7x8Xt-WVzffPz6vz7dWOZELLpfb8E1vXCCWsEA8OcAOvazlLWVqEs9LA0hLXS-ZZ7xyRznjjFuVM9EewIfd7NXaf4d4Zc9Bjy9nYzQZyzppJLwbstKHagTTHnBF6vUxhN2mhK9DYA_RKA3rqrqdIvAWhZ-073C-Z-BPfWtXO81j_t6yZbM_jqqw35FeNCcMXYG7YKd6unkED3IdoVjLqVS82krmsVZf8Bg7udWA</recordid><startdate>19921225</startdate><enddate>19921225</enddate><creator>KITAJIMA, I</creator><creator>SHINOHARA, T</creator><creator>MINOR, T</creator><creator>BIBBS, L</creator><creator>BILAKOVICS, J</creator><creator>NERENBERG, M</creator><general>American Society for Biochemistry and Molecular Biology</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>7TM</scope><scope>7U9</scope><scope>H94</scope></search><sort><creationdate>19921225</creationdate><title>Human T-cell leukemia virus type I tax transformation is associated with increased uptake of oligodeoxynucleotides in vitro and in vivo</title><author>KITAJIMA, I ; SHINOHARA, T ; MINOR, T ; BIBBS, L ; BILAKOVICS, J ; NERENBERG, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3556-bfb7e39b5d5ca53ea3d5ecd29c132a3d8cebe7a0326df24fd363df0d844d8b053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>3T3 Cells</topic><topic>Action of physical and chemical agents</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Biological Transport</topic><topic>Blotting, Northern</topic><topic>Cell Line</topic><topic>Cell Transformation, Neoplastic</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genes, pX - drug effects</topic><topic>Human T-lymphotropic virus 1 - drug effects</topic><topic>Human T-lymphotropic virus 1 - genetics</topic><topic>Kinetics</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred DBA</topic><topic>Mice, Transgenic</topic><topic>Microbiology</topic><topic>Molecular Sequence Data</topic><topic>Oligodeoxyribonucleotides - metabolism</topic><topic>Oligodeoxyribonucleotides - pharmacology</topic><topic>Oligonucleotides, Antisense - metabolism</topic><topic>Oligonucleotides, Antisense - pharmacology</topic><topic>Organ Specificity</topic><topic>Repetitive Sequences, Nucleic Acid</topic><topic>RNA - genetics</topic><topic>RNA - isolation & purification</topic><topic>Transcriptional Activation - drug effects</topic><topic>Virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KITAJIMA, I</creatorcontrib><creatorcontrib>SHINOHARA, T</creatorcontrib><creatorcontrib>MINOR, T</creatorcontrib><creatorcontrib>BIBBS, L</creatorcontrib><creatorcontrib>BILAKOVICS, J</creatorcontrib><creatorcontrib>NERENBERG, M</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>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KITAJIMA, I</au><au>SHINOHARA, T</au><au>MINOR, T</au><au>BIBBS, L</au><au>BILAKOVICS, J</au><au>NERENBERG, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human T-cell leukemia virus type I tax transformation is associated with increased uptake of oligodeoxynucleotides in vitro and in vivo</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1992-12-25</date><risdate>1992</risdate><volume>267</volume><issue>36</issue><spage>25881</spage><epage>25888</epage><pages>25881-25888</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><coden>JBCHA3</coden><abstract>We have utilized antisense oligodeoxynucleotides (ODNs) to modulate transcriptional activation by the human T-cell leukemia
virus type I (HTLV-I) tax gene, the major transcriptional regulator of this virus. 3'-Terminal phosphorothioate-modified antisense
ODNs were shown to efficiently inhibit Tax protein expression both in vitro and in vivo. Terminal substitution did not affect
the affinity of ODNs for their target sequence but conferred a 9-fold increase in tax inhibition in vitro. When delivered
into mice by intraperitoneal injection, ODNs inhibited tax expression in established tumors by 90%. Unmanipulated tax-transformed
mouse fibroblasts, or HTLV-I-transformed human lymphocytes, showed at least 5-fold higher ODN binding and uptake over control
cells. Balb/3T3 cell binding was induced to similar levels by cellular activators. This suggests that constitutive activation
by tax transformation may increase susceptibility of HTLV-I-transformed cells to antisense therapy, providing a rationale
for the use of antisense ODN therapeutics in HTLV-I-associated diseases.</abstract><cop>Bethesda, MD</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>1281476</pmid><doi>10.1016/S0021-9258(18)35691-6</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 0021-9258 1083-351X |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | 3T3 Cells Action of physical and chemical agents Animals Base Sequence Biological and medical sciences Biological Transport Blotting, Northern Cell Line Cell Transformation, Neoplastic Female Fundamental and applied biological sciences. Psychology Genes, pX - drug effects Human T-lymphotropic virus 1 - drug effects Human T-lymphotropic virus 1 - genetics Kinetics Male Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Transgenic Microbiology Molecular Sequence Data Oligodeoxyribonucleotides - metabolism Oligodeoxyribonucleotides - pharmacology Oligonucleotides, Antisense - metabolism Oligonucleotides, Antisense - pharmacology Organ Specificity Repetitive Sequences, Nucleic Acid RNA - genetics RNA - isolation & purification Transcriptional Activation - drug effects Virology |
| title | Human T-cell leukemia virus type I tax transformation is associated with increased uptake of oligodeoxynucleotides in vitro and in vivo |
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