Retinoid Receptor Antisense DNAs Inhibit Alkaline Phosphatase Induction and Clonogenicity in Malignant Keratinocytes
Antisense oligodeoxynucleotides [oligo(dN)s] corresponding to human cellular retinol-binding protein I (cRBP) and human nuclear retinoic acid receptor α (hnRAR) were synthesized. Exposure of human malignant keratinocytes to these oligo(dN)s significantly attenuated the level of cytoplasmic cRBP and...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1989-07, Vol.86 (14), p.5590-5594 |
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| creator | Cope, Frederick O. Wille, John J. |
| description | Antisense oligodeoxynucleotides [oligo(dN)s] corresponding to human cellular retinol-binding protein I (cRBP) and human nuclear retinoic acid receptor α (hnRAR) were synthesized. Exposure of human malignant keratinocytes to these oligo(dN)s significantly attenuated the level of cytoplasmic cRBP and hnRAR in a concentration- and time-dependent manner. Further, the induction of alkaline phosphatase by retinol in these cells was blocked by treatment with 30 μ M antisense oligo(dN) to cRBP or hnRAR but not by 30 μ M of sense oligo(dN) to cRBP. Antisense oligo(dN) treatments concomitantly induced cell rounding, loss of cell-cell attachment, and cell adhesion to the substratum. By contrast, treatment of cells with an anticytokinetic agent, cytochalasin B, or with a cytostatic concentration of sodium azide failed to reduce cytoplasmic cRBP or hnRAR from nuclear extracts, even though antisense oligo(dN)-like changes in cell morphology were observed. Treatment of the cells for >2.75 hr with 20-40 μ M of either antisense oligo(dN) also led to the loss of clonogenic potential. These results show that both cytoplasmic and nuclear receptors for retinoids are important in the transduction of a retinoid signal response critical to cellular growth and differentiation. Our findings also suggest that defined genes, which are specified by retinoids and their receptors, may account for the pleiotropic effect of vitamin A compounds. |
| doi_str_mv | 10.1073/pnas.86.14.5590 |
| format | Article |
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Exposure of human malignant keratinocytes to these oligo(dN)s significantly attenuated the level of cytoplasmic cRBP and hnRAR in a concentration- and time-dependent manner. Further, the induction of alkaline phosphatase by retinol in these cells was blocked by treatment with 30 μ M antisense oligo(dN) to cRBP or hnRAR but not by 30 μ M of sense oligo(dN) to cRBP. Antisense oligo(dN) treatments concomitantly induced cell rounding, loss of cell-cell attachment, and cell adhesion to the substratum. By contrast, treatment of cells with an anticytokinetic agent, cytochalasin B, or with a cytostatic concentration of sodium azide failed to reduce cytoplasmic cRBP or hnRAR from nuclear extracts, even though antisense oligo(dN)-like changes in cell morphology were observed. Treatment of the cells for >2.75 hr with 20-40 μ M of either antisense oligo(dN) also led to the loss of clonogenic potential. These results show that both cytoplasmic and nuclear receptors for retinoids are important in the transduction of a retinoid signal response critical to cellular growth and differentiation. Our findings also suggest that defined genes, which are specified by retinoids and their receptors, may account for the pleiotropic effect of vitamin A compounds.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.86.14.5590</identifier><identifier>PMID: 2546159</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>Alkaline Phosphatase - biosynthesis ; Base Sequence ; Biological and medical sciences ; Carcinoma, Squamous Cell ; Carrier Proteins - genetics ; Carrier Proteins - physiology ; Cell culture techniques ; Cell differentiation, maturation, development, hematopoiesis ; Cell growth ; Cell nucleus ; Cell physiology ; Cells ; Cytoplasm ; Enzyme Induction ; Epidermis ; Fundamental and applied biological sciences. Psychology ; Humans ; Keratinocytes ; Legends ; Molecular and cellular biology ; Neoplasm Proteins - genetics ; Oligonucleotides - pharmacology ; Oligonucleotides, Antisense ; Phosphatases ; Receptors ; Receptors, Retinoic Acid ; Retinoids ; Retinol-Binding Proteins - genetics ; Retinol-Binding Proteins, Cellular ; Tongue Neoplasms ; Tumor Stem Cell Assay</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1989-07, Vol.86 (14), p.5590-5594</ispartof><rights>1990 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-d409fe7ff2d3683fb22d495fdec41af69ad916720dd615c1ef10581824cb2e53</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/86/14.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/34527$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/34527$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=6955230$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2546159$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cope, Frederick O.</creatorcontrib><creatorcontrib>Wille, John J.</creatorcontrib><title>Retinoid Receptor Antisense DNAs Inhibit Alkaline Phosphatase Induction and Clonogenicity in Malignant Keratinocytes</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Antisense oligodeoxynucleotides [oligo(dN)s] corresponding to human cellular retinol-binding protein I (cRBP) and human nuclear retinoic acid receptor α (hnRAR) were synthesized. Exposure of human malignant keratinocytes to these oligo(dN)s significantly attenuated the level of cytoplasmic cRBP and hnRAR in a concentration- and time-dependent manner. Further, the induction of alkaline phosphatase by retinol in these cells was blocked by treatment with 30 μ M antisense oligo(dN) to cRBP or hnRAR but not by 30 μ M of sense oligo(dN) to cRBP. Antisense oligo(dN) treatments concomitantly induced cell rounding, loss of cell-cell attachment, and cell adhesion to the substratum. By contrast, treatment of cells with an anticytokinetic agent, cytochalasin B, or with a cytostatic concentration of sodium azide failed to reduce cytoplasmic cRBP or hnRAR from nuclear extracts, even though antisense oligo(dN)-like changes in cell morphology were observed. Treatment of the cells for >2.75 hr with 20-40 μ M of either antisense oligo(dN) also led to the loss of clonogenic potential. These results show that both cytoplasmic and nuclear receptors for retinoids are important in the transduction of a retinoid signal response critical to cellular growth and differentiation. Our findings also suggest that defined genes, which are specified by retinoids and their receptors, may account for the pleiotropic effect of vitamin A compounds.</description><subject>Alkaline Phosphatase - biosynthesis</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Squamous Cell</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - physiology</subject><subject>Cell culture techniques</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell growth</subject><subject>Cell nucleus</subject><subject>Cell physiology</subject><subject>Cells</subject><subject>Cytoplasm</subject><subject>Enzyme Induction</subject><subject>Epidermis</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Keratinocytes</subject><subject>Legends</subject><subject>Molecular and cellular biology</subject><subject>Neoplasm Proteins - genetics</subject><subject>Oligonucleotides - pharmacology</subject><subject>Oligonucleotides, Antisense</subject><subject>Phosphatases</subject><subject>Receptors</subject><subject>Receptors, Retinoic Acid</subject><subject>Retinoids</subject><subject>Retinol-Binding Proteins - genetics</subject><subject>Retinol-Binding Proteins, Cellular</subject><subject>Tongue Neoplasms</subject><subject>Tumor Stem Cell Assay</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1989</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9ks2vEyEUxYnRPGt1bWKiYWF01T5gYGZYuGjqV-PzIy9vTyhcWp5TmDdQY_97mbRW3bhicX7nnntzQOgpJXNKmuqyDzrN23pO-VwISe6hCSWSzmouyX00IYQ1s5Yz_hA9SumWECJFSy7QBRO8pkJOUL6G7EP0Fl-DgT7HAS9C9glCAvz2yyLhVdj6tc940X3XnQ-Av21j6rc660Ksgt2b7GPAOli87GKIGwje-HzAPuDPxbEJOmT8CQY9BplDhvQYPXC6S_Dk9E7Rzft3N8uPs6uvH1bLxdXMlPXzzHIiHTTOMVvVbeXWjFkuhbNgONWultpKWjeMWFuOMRQcJaKlLeNmzUBUU_TmOLbfr3dgDYQ86E71g9_p4aCi9upfJfit2sQfismmLoFT9OrkH-LdHlJWO58MdJ0OEPdJUcFJ1ZC6gJdH0AwxpQHcOYMSNdakxppUWyvK1VhTcTz_e7Uzf-ql6C9Puk5Gd27Qwfh0xmopBKvGMa9P2Dj_t_onR7l912X4mQv54r9kAZ4dgdtUPsGZqLhgTfULG8y_iQ</recordid><startdate>19890701</startdate><enddate>19890701</enddate><creator>Cope, Frederick O.</creator><creator>Wille, John J.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>19890701</creationdate><title>Retinoid Receptor Antisense DNAs Inhibit Alkaline Phosphatase Induction and Clonogenicity in Malignant Keratinocytes</title><author>Cope, Frederick O. ; Wille, John J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-d409fe7ff2d3683fb22d495fdec41af69ad916720dd615c1ef10581824cb2e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1989</creationdate><topic>Alkaline Phosphatase - biosynthesis</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Squamous Cell</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - physiology</topic><topic>Cell culture techniques</topic><topic>Cell differentiation, maturation, development, hematopoiesis</topic><topic>Cell growth</topic><topic>Cell nucleus</topic><topic>Cell physiology</topic><topic>Cells</topic><topic>Cytoplasm</topic><topic>Enzyme Induction</topic><topic>Epidermis</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Keratinocytes</topic><topic>Legends</topic><topic>Molecular and cellular biology</topic><topic>Neoplasm Proteins - genetics</topic><topic>Oligonucleotides - pharmacology</topic><topic>Oligonucleotides, Antisense</topic><topic>Phosphatases</topic><topic>Receptors</topic><topic>Receptors, Retinoic Acid</topic><topic>Retinoids</topic><topic>Retinol-Binding Proteins - genetics</topic><topic>Retinol-Binding Proteins, Cellular</topic><topic>Tongue Neoplasms</topic><topic>Tumor Stem Cell Assay</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cope, Frederick O.</creatorcontrib><creatorcontrib>Wille, John 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>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cope, Frederick O.</au><au>Wille, John J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Retinoid Receptor Antisense DNAs Inhibit Alkaline Phosphatase Induction and Clonogenicity in Malignant Keratinocytes</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1989-07-01</date><risdate>1989</risdate><volume>86</volume><issue>14</issue><spage>5590</spage><epage>5594</epage><pages>5590-5594</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>Antisense oligodeoxynucleotides [oligo(dN)s] corresponding to human cellular retinol-binding protein I (cRBP) and human nuclear retinoic acid receptor α (hnRAR) were synthesized. Exposure of human malignant keratinocytes to these oligo(dN)s significantly attenuated the level of cytoplasmic cRBP and hnRAR in a concentration- and time-dependent manner. Further, the induction of alkaline phosphatase by retinol in these cells was blocked by treatment with 30 μ M antisense oligo(dN) to cRBP or hnRAR but not by 30 μ M of sense oligo(dN) to cRBP. Antisense oligo(dN) treatments concomitantly induced cell rounding, loss of cell-cell attachment, and cell adhesion to the substratum. By contrast, treatment of cells with an anticytokinetic agent, cytochalasin B, or with a cytostatic concentration of sodium azide failed to reduce cytoplasmic cRBP or hnRAR from nuclear extracts, even though antisense oligo(dN)-like changes in cell morphology were observed. Treatment of the cells for >2.75 hr with 20-40 μ M of either antisense oligo(dN) also led to the loss of clonogenic potential. These results show that both cytoplasmic and nuclear receptors for retinoids are important in the transduction of a retinoid signal response critical to cellular growth and differentiation. Our findings also suggest that defined genes, which are specified by retinoids and their receptors, may account for the pleiotropic effect of vitamin A compounds.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>2546159</pmid><doi>10.1073/pnas.86.14.5590</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1989-07, Vol.86 (14), p.5590-5594 |
| issn | 0027-8424 1091-6490 |
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| recordid | cdi_jstor_primary_34527 |
| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Alkaline Phosphatase - biosynthesis Base Sequence Biological and medical sciences Carcinoma, Squamous Cell Carrier Proteins - genetics Carrier Proteins - physiology Cell culture techniques Cell differentiation, maturation, development, hematopoiesis Cell growth Cell nucleus Cell physiology Cells Cytoplasm Enzyme Induction Epidermis Fundamental and applied biological sciences. Psychology Humans Keratinocytes Legends Molecular and cellular biology Neoplasm Proteins - genetics Oligonucleotides - pharmacology Oligonucleotides, Antisense Phosphatases Receptors Receptors, Retinoic Acid Retinoids Retinol-Binding Proteins - genetics Retinol-Binding Proteins, Cellular Tongue Neoplasms Tumor Stem Cell Assay |
| title | Retinoid Receptor Antisense DNAs Inhibit Alkaline Phosphatase Induction and Clonogenicity in Malignant Keratinocytes |
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