Evaluation of N-ras oncogene anti-sense, sense and nonsense sequence methylphosphonate oligonucleotide analogues.
Identifieur interne : 000D00 ( Ncbi/Merge ); précédent : 000C99; suivant : 000D01Evaluation of N-ras oncogene anti-sense, sense and nonsense sequence methylphosphonate oligonucleotide analogues.
Auteurs : D M Tidd ; P. Hawley ; H M Warenius ; I. GibsonSource :
- Anti-cancer drug design [ 0266-9536 ] ; 1988.
Descripteurs français
- KwdFr :
- ARN, ARN complémentaire, Cellules cancéreuses en culture, Codon, Dexaméthasone (pharmacologie), Humains, Hybridation d'acides nucléiques, Lignée cellulaire (), Oligonucléotides (pharmacologie), Oncogènes, Protéines proto-oncogènes (biosynthèse), Protéines proto-oncogènes p21(ras), Séquence nucléotidique.
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , biosynthesis : Proto-Oncogene Proteins.
- chemical , pharmacology : Dexamethasone, Oligonucleotides.
- chemical : Codon, Proto-Oncogene Proteins p21(ras), RNA, RNA, Complementary.
- drug effects : Cell Line.
- Base Sequence, Humans, Nucleic Acid Hybridization, Oncogenes, Tumor Cells, Cultured.
Abstract
We have investigated the potential for using anti-sense non-ionic methylphosphonate oligonucleotide analogues to study the relationship between oncogene expression and maintenance of the transformed phenotype in malignant cells. Our results confirmed that the methylphosphonates are resistant to biochemical degradation and are devoid of non-specific toxicity towards cultured human HT29 cells. At low temperature (less than 5 degrees C) both N-ras anti-sense and nonsense analogue 9-mers formed 1:1 complexes in solution with an N-ras sense phosphodiester oligodeoxynucleotide 20-mer, but these were largely dissociated at 25 degrees C. Only a fraction (10-20%) of the anti-sense molecules formed stable sequence specific hybrids (Tm 34 degrees C) with the 20-mer. The biological activity of the oligonucleotide analogues was tested in cell culture at 37 degrees C using T15 cells, a line of NIH 3T3 cells transfected with multiple copies of the human N-ras oncogene under control of the glucocorticoid inducible MMTV promoter. On balance the N-ras anti-sense methylphosphonate 9-mer (20-80 microM) had no effect on these cells. In only one of five experiments was an apparent reduction in dexamethasone-induced p21N-ras protein accumulation observed in the presence of the oligonucleotide analogue. Also without effect was an anti-sense 20-mer consisting of a phosphodiester sequence bounded by two methylphosphonate linkages at each end (25-50 microM in culture media; 4.8 microM by microinjection). We conclude from these experiments that, in order to achieve pronounced effects on oncogene expression, it may be necessary to use longer anti-sense methylphosphonate chains, affinity purified for their ability to hybridize with the target sequences.
PubMed: 2457379
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Evaluation of N-ras oncogene anti-sense, sense and nonsense sequence methylphosphonate oligonucleotide analogues.</title><author><name sortKey="Tidd, D M" sort="Tidd, D M" uniqKey="Tidd D" first="D M" last="Tidd">D M Tidd</name><affiliation><nlm:affiliation>Cancer Research Campaign Department of Radiation Oncology, University of Liverpool.</nlm:affiliation><wicri:noCountry code="subField">University of Liverpool</wicri:noCountry></affiliation></author><author><name sortKey="Hawley, P" sort="Hawley, P" uniqKey="Hawley P" first="P" last="Hawley">P. Hawley</name></author><author><name sortKey="Warenius, H M" sort="Warenius, H M" uniqKey="Warenius H" first="H M" last="Warenius">H M Warenius</name></author><author><name sortKey="Gibson, I" sort="Gibson, I" uniqKey="Gibson I" first="I" last="Gibson">I. Gibson</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1988">1988</date><idno type="RBID">pubmed:2457379</idno><idno type="pmid">2457379</idno><idno type="wicri:Area/PubMed/Corpus">002A57</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002A57</idno><idno type="wicri:Area/PubMed/Curation">002A57</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002A57</idno><idno type="wicri:Area/PubMed/Checkpoint">002902</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002902</idno><idno type="wicri:Area/Ncbi/Merge">000D00</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Evaluation of N-ras oncogene anti-sense, sense and nonsense sequence methylphosphonate oligonucleotide analogues.</title><author><name sortKey="Tidd, D M" sort="Tidd, D M" uniqKey="Tidd D" first="D M" last="Tidd">D M Tidd</name><affiliation><nlm:affiliation>Cancer Research Campaign Department of Radiation Oncology, University of Liverpool.</nlm:affiliation><wicri:noCountry code="subField">University of Liverpool</wicri:noCountry></affiliation></author><author><name sortKey="Hawley, P" sort="Hawley, P" uniqKey="Hawley P" first="P" last="Hawley">P. Hawley</name></author><author><name sortKey="Warenius, H M" sort="Warenius, H M" uniqKey="Warenius H" first="H M" last="Warenius">H M Warenius</name></author><author><name sortKey="Gibson, I" sort="Gibson, I" uniqKey="Gibson I" first="I" last="Gibson">I. Gibson</name></author></analytic><series><title level="j">Anti-cancer drug design</title><idno type="ISSN">0266-9536</idno><imprint><date when="1988" type="published">1988</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Base Sequence</term><term>Cell Line (drug effects)</term><term>Codon</term><term>Dexamethasone (pharmacology)</term><term>Humans</term><term>Nucleic Acid Hybridization</term><term>Oligonucleotides (pharmacology)</term><term>Oncogenes</term><term>Proto-Oncogene Proteins (biosynthesis)</term><term>Proto-Oncogene Proteins p21(ras)</term><term>RNA</term><term>RNA, Complementary</term><term>Tumor Cells, Cultured</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN</term><term>ARN complémentaire</term><term>Cellules cancéreuses en culture</term><term>Codon</term><term>Dexaméthasone (pharmacologie)</term><term>Humains</term><term>Hybridation d'acides nucléiques</term><term>Lignée cellulaire ()</term><term>Oligonucléotides (pharmacologie)</term><term>Oncogènes</term><term>Protéines proto-oncogènes (biosynthèse)</term><term>Protéines proto-oncogènes p21(ras)</term><term>Séquence nucléotidique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Proto-Oncogene Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Dexamethasone</term><term>Oligonucleotides</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Codon</term><term>Proto-Oncogene Proteins p21(ras)</term><term>RNA</term><term>RNA, Complementary</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Protéines proto-oncogènes</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Line</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Dexaméthasone</term><term>Oligonucléotides</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Base Sequence</term><term>Humans</term><term>Nucleic Acid Hybridization</term><term>Oncogenes</term><term>Tumor Cells, Cultured</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>ARN</term><term>ARN complémentaire</term><term>Cellules cancéreuses en culture</term><term>Codon</term><term>Humains</term><term>Hybridation d'acides nucléiques</term><term>Lignée cellulaire</term><term>Oncogènes</term><term>Protéines proto-oncogènes p21(ras)</term><term>Séquence nucléotidique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We have investigated the potential for using anti-sense non-ionic methylphosphonate oligonucleotide analogues to study the relationship between oncogene expression and maintenance of the transformed phenotype in malignant cells. Our results confirmed that the methylphosphonates are resistant to biochemical degradation and are devoid of non-specific toxicity towards cultured human HT29 cells. At low temperature (less than 5 degrees C) both N-ras anti-sense and nonsense analogue 9-mers formed 1:1 complexes in solution with an N-ras sense phosphodiester oligodeoxynucleotide 20-mer, but these were largely dissociated at 25 degrees C. Only a fraction (10-20%) of the anti-sense molecules formed stable sequence specific hybrids (Tm 34 degrees C) with the 20-mer. The biological activity of the oligonucleotide analogues was tested in cell culture at 37 degrees C using T15 cells, a line of NIH 3T3 cells transfected with multiple copies of the human N-ras oncogene under control of the glucocorticoid inducible MMTV promoter. On balance the N-ras anti-sense methylphosphonate 9-mer (20-80 microM) had no effect on these cells. In only one of five experiments was an apparent reduction in dexamethasone-induced p21N-ras protein accumulation observed in the presence of the oligonucleotide analogue. Also without effect was an anti-sense 20-mer consisting of a phosphodiester sequence bounded by two methylphosphonate linkages at each end (25-50 microM in culture media; 4.8 microM by microinjection). We conclude from these experiments that, in order to achieve pronounced effects on oncogene expression, it may be necessary to use longer anti-sense methylphosphonate chains, affinity purified for their ability to hybridize with the target sequences.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">2457379</PMID><DateCompleted><Year>1988</Year><Month>09</Month><Day>28</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0266-9536</ISSN><JournalIssue CitedMedium="Print"><Volume>3</Volume><Issue>2</Issue><PubDate><Year>1988</Year><Month>Aug</Month></PubDate></JournalIssue><Title>Anti-cancer drug design</Title><ISOAbbreviation>Anticancer Drug Des.</ISOAbbreviation></Journal><ArticleTitle>Evaluation of N-ras oncogene anti-sense, sense and nonsense sequence methylphosphonate oligonucleotide analogues.</ArticleTitle><Pagination><MedlinePgn>117-27</MedlinePgn></Pagination><Abstract><AbstractText>We have investigated the potential for using anti-sense non-ionic methylphosphonate oligonucleotide analogues to study the relationship between oncogene expression and maintenance of the transformed phenotype in malignant cells. Our results confirmed that the methylphosphonates are resistant to biochemical degradation and are devoid of non-specific toxicity towards cultured human HT29 cells. At low temperature (less than 5 degrees C) both N-ras anti-sense and nonsense analogue 9-mers formed 1:1 complexes in solution with an N-ras sense phosphodiester oligodeoxynucleotide 20-mer, but these were largely dissociated at 25 degrees C. Only a fraction (10-20%) of the anti-sense molecules formed stable sequence specific hybrids (Tm 34 degrees C) with the 20-mer. The biological activity of the oligonucleotide analogues was tested in cell culture at 37 degrees C using T15 cells, a line of NIH 3T3 cells transfected with multiple copies of the human N-ras oncogene under control of the glucocorticoid inducible MMTV promoter. On balance the N-ras anti-sense methylphosphonate 9-mer (20-80 microM) had no effect on these cells. In only one of five experiments was an apparent reduction in dexamethasone-induced p21N-ras protein accumulation observed in the presence of the oligonucleotide analogue. Also without effect was an anti-sense 20-mer consisting of a phosphodiester sequence bounded by two methylphosphonate linkages at each end (25-50 microM in culture media; 4.8 microM by microinjection). We conclude from these experiments that, in order to achieve pronounced effects on oncogene expression, it may be necessary to use longer anti-sense methylphosphonate chains, affinity purified for their ability to hybridize with the target sequences.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tidd</LastName><ForeName>D M</ForeName><Initials>DM</Initials><AffiliationInfo><Affiliation>Cancer Research Campaign Department of Radiation Oncology, University of Liverpool.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hawley</LastName><ForeName>P</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Warenius</LastName><ForeName>H M</ForeName><Initials>HM</Initials></Author><Author ValidYN="Y"><LastName>Gibson</LastName><ForeName>I</ForeName><Initials>I</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Anticancer Drug Des</MedlineTA><NlmUniqueID>8603523</NlmUniqueID><ISSNLinking>0266-9536</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D003062">Codon</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009841">Oligonucleotides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011518">Proto-Oncogene Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018075">RNA, Complementary</NameOfSubstance></Chemical><Chemical><RegistryNumber>63231-63-0</RegistryNumber><NameOfSubstance UI="D012313">RNA</NameOfSubstance></Chemical><Chemical><RegistryNumber>7S5I7G3JQL</RegistryNumber><NameOfSubstance UI="D003907">Dexamethasone</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.6.5.2</RegistryNumber><NameOfSubstance UI="C501009">HRAS protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.6.5.2</RegistryNumber><NameOfSubstance UI="D016283">Proto-Oncogene Proteins p21(ras)</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D001483" MajorTopicYN="N">Base Sequence</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003062" MajorTopicYN="N">Codon</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003907" MajorTopicYN="N">Dexamethasone</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009693" MajorTopicYN="N">Nucleic Acid Hybridization</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009841" MajorTopicYN="N">Oligonucleotides</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009857" MajorTopicYN="Y">Oncogenes</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011518" MajorTopicYN="N">Proto-Oncogene Proteins</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="Y">biosynthesis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016283" MajorTopicYN="N">Proto-Oncogene Proteins p21(ras)</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012313" MajorTopicYN="N">RNA</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018075" MajorTopicYN="N">RNA, Complementary</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014407" MajorTopicYN="N">Tumor Cells, Cultured</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1988</Year><Month>8</Month><Day>1</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1988</Year><Month>8</Month><Day>1</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1988</Year><Month>8</Month><Day>1</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">2457379</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list></list><tree><noCountry><name sortKey="Gibson, I" sort="Gibson, I" uniqKey="Gibson I" first="I" last="Gibson">I. Gibson</name><name sortKey="Hawley, P" sort="Hawley, P" uniqKey="Hawley P" first="P" last="Hawley">P. Hawley</name><name sortKey="Tidd, D M" sort="Tidd, D M" uniqKey="Tidd D" first="D M" last="Tidd">D M Tidd</name><name sortKey="Warenius, H M" sort="Warenius, H M" uniqKey="Warenius H" first="H M" last="Warenius">H M Warenius</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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