Loading…
Telomerase-Driven Expression of the Sodium Iodide Symporter (NIS) for in Vivo Radioiodide Treatment of Cancer: A New Broad-Spectrum NIS-Mediated Antitumor Approach
Context: Telomerase promoters (hTERT and hTR) are useful for transcriptional targeting in gene therapy models of cancer. Telomerase-driven expression of the sodium iodide symporter (NIS) in tumor cells has been successfully used as a reporter gene in vivo using positron emission tomography (PET) ima...
Saved in:
| Published in: | The journal of clinical endocrinology and metabolism 2011-09, Vol.96 (9), p.E1435-E1443 |
|---|---|
| Main Authors: | , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c4506-21c29b4fd6fa245b2f5c1616fb19326b71e31aae842743f8ba989efc95d98c1b3 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c4506-21c29b4fd6fa245b2f5c1616fb19326b71e31aae842743f8ba989efc95d98c1b3 |
| container_end_page | E1443 |
| container_issue | 9 |
| container_start_page | E1435 |
| container_title | The journal of clinical endocrinology and metabolism |
| container_volume | 96 |
| creator | Riesco-Eizaguirre, Garcilaso De la Vieja, Antonio Rodríguez, Irene Miranda, Soledad Martín-Duque, Pilar Vassaux, Georges Santisteban, Pilar |
| description | Context:
Telomerase promoters (hTERT and hTR) are useful for transcriptional targeting in gene therapy models of cancer. Telomerase-driven expression of the sodium iodide symporter (NIS) in tumor cells has been successfully used as a reporter gene in vivo using positron emission tomography (PET) imaging.
Objective:
The aim of this study was to investigate the NIS-mediated therapeutic effect of telomerase promoters in a wide variety of human cancer cell lines.
Design and Methods:
Promoter fragments from either hTERT or hTR were used to drive the expression of NIS in cell lines derived from melanoma (M14), breast (MDA-MB-231), colon (HT-29), lung (H460), ovarian (OVCAR-3), and thyroid (TPC-1) carcinomas. Iodide uptake assays, protein immunodetection, and clonigenic assays were used to confirm NIS functional expression and the 131I-mediated cytopathic effect. Tumor xenografts in mice were infected with hTERT and hTR and then treated using radioiodide.
Results:
Both promoters were selectively active in cancer cells that were effectively killed by exposure to 131I. One single dose of 1 mCi 131I markedly suppressed tumor growth of melanoma-derived tumor xenografts compared with controls. This effect was more modest in colon cancer-derived xenografts in part due to the reduced infectivity and the tumor cystic nature. The therapeutic effect of hTR promoter was found to be stronger than that of hTERT promoter.
Conclusions:
These results demonstrate that telomerase-driven expression of NIS could potentially have applications for 131I therapy of a wide variety of cancers. Additionally, this is the first study to report NIS-mediated 131I therapy of melanoma tumors in vivo. |
| doi_str_mv | 10.1210/jc.2010-2373 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_888091595</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1221134158</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4506-21c29b4fd6fa245b2f5c1616fb19326b71e31aae842743f8ba989efc95d98c1b3</originalsourceid><addsrcrecordid>eNp9kcFu1DAQhiMEokvhxhn5RpFw8ThxEve2LAVWKkViF8TNcpyJ1ksSBzvp0ufhRfGSwglhyRqN9c1ny3-SPAV2DhzYq7055wwY5WmR3ksWIDNBC5DF_WTBGAcqC_71JHkUwp4xyDKRPkxOOOTxWKSL5OcWW9eh1wHpG29vsCeXPwaPIVjXE9eQcYdk42o7dWQdSx27225wfkRPzq7XmxekcZ7YnnyxN4580rV1dua2HvXYYT8eNSvdG_QXZEmu8UBee6druhnQjD6Ko4Z-wNrqEWuy7Ec7Tl2ULochcmb3OHnQ6Dbgk7t6mnx-e7ldvadXH9-tV8srajLBcsrBcFllTZ03mmei4o0wkEPeVCBTnlcFYApaY5nxIkubstKylNgYKWpZGqjS0-T57I3Xfp8wjKqzwWDb6h7dFFRZlkyCkCKSZ_8lgXOANANRRvTljBrvQvDYqMHbTvtbBUwdA1R7o44BqmOAEX92Z56qDuu_8J_EIpDNwMG1MYPwrZ0O6NUOdTvuFIsry4uSRiMwGTsat8jjWDqPYV87422Pv0NWezf5Pn7qv1_zC_zTt0I</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1221134158</pqid></control><display><type>article</type><title>Telomerase-Driven Expression of the Sodium Iodide Symporter (NIS) for in Vivo Radioiodide Treatment of Cancer: A New Broad-Spectrum NIS-Mediated Antitumor Approach</title><source>Oxford Journals Online</source><creator>Riesco-Eizaguirre, Garcilaso ; De la Vieja, Antonio ; Rodríguez, Irene ; Miranda, Soledad ; Martín-Duque, Pilar ; Vassaux, Georges ; Santisteban, Pilar</creator><creatorcontrib>Riesco-Eizaguirre, Garcilaso ; De la Vieja, Antonio ; Rodríguez, Irene ; Miranda, Soledad ; Martín-Duque, Pilar ; Vassaux, Georges ; Santisteban, Pilar</creatorcontrib><description>Context:
Telomerase promoters (hTERT and hTR) are useful for transcriptional targeting in gene therapy models of cancer. Telomerase-driven expression of the sodium iodide symporter (NIS) in tumor cells has been successfully used as a reporter gene in vivo using positron emission tomography (PET) imaging.
Objective:
The aim of this study was to investigate the NIS-mediated therapeutic effect of telomerase promoters in a wide variety of human cancer cell lines.
Design and Methods:
Promoter fragments from either hTERT or hTR were used to drive the expression of NIS in cell lines derived from melanoma (M14), breast (MDA-MB-231), colon (HT-29), lung (H460), ovarian (OVCAR-3), and thyroid (TPC-1) carcinomas. Iodide uptake assays, protein immunodetection, and clonigenic assays were used to confirm NIS functional expression and the 131I-mediated cytopathic effect. Tumor xenografts in mice were infected with hTERT and hTR and then treated using radioiodide.
Results:
Both promoters were selectively active in cancer cells that were effectively killed by exposure to 131I. One single dose of 1 mCi 131I markedly suppressed tumor growth of melanoma-derived tumor xenografts compared with controls. This effect was more modest in colon cancer-derived xenografts in part due to the reduced infectivity and the tumor cystic nature. The therapeutic effect of hTR promoter was found to be stronger than that of hTERT promoter.
Conclusions:
These results demonstrate that telomerase-driven expression of NIS could potentially have applications for 131I therapy of a wide variety of cancers. Additionally, this is the first study to report NIS-mediated 131I therapy of melanoma tumors in vivo.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2010-2373</identifier><identifier>PMID: 21697253</identifier><language>eng</language><publisher>United States: Endocrine Society</publisher><subject>Animal models ; Animals ; Cell Line, Tumor ; Genetic Therapy - methods ; Humans ; Iodine Radioisotopes - therapeutic use ; Mice ; Neoplasm Transplantation ; Neoplasms - genetics ; Neoplasms - metabolism ; Neoplasms - radiotherapy ; Promoter Regions, Genetic ; Symporters - genetics ; Symporters - metabolism ; Telomerase - genetics ; Telomerase - metabolism</subject><ispartof>The journal of clinical endocrinology and metabolism, 2011-09, Vol.96 (9), p.E1435-E1443</ispartof><rights>Copyright © 2011 by The Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4506-21c29b4fd6fa245b2f5c1616fb19326b71e31aae842743f8ba989efc95d98c1b3</citedby><cites>FETCH-LOGICAL-c4506-21c29b4fd6fa245b2f5c1616fb19326b71e31aae842743f8ba989efc95d98c1b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21697253$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Riesco-Eizaguirre, Garcilaso</creatorcontrib><creatorcontrib>De la Vieja, Antonio</creatorcontrib><creatorcontrib>Rodríguez, Irene</creatorcontrib><creatorcontrib>Miranda, Soledad</creatorcontrib><creatorcontrib>Martín-Duque, Pilar</creatorcontrib><creatorcontrib>Vassaux, Georges</creatorcontrib><creatorcontrib>Santisteban, Pilar</creatorcontrib><title>Telomerase-Driven Expression of the Sodium Iodide Symporter (NIS) for in Vivo Radioiodide Treatment of Cancer: A New Broad-Spectrum NIS-Mediated Antitumor Approach</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Context:
Telomerase promoters (hTERT and hTR) are useful for transcriptional targeting in gene therapy models of cancer. Telomerase-driven expression of the sodium iodide symporter (NIS) in tumor cells has been successfully used as a reporter gene in vivo using positron emission tomography (PET) imaging.
Objective:
The aim of this study was to investigate the NIS-mediated therapeutic effect of telomerase promoters in a wide variety of human cancer cell lines.
Design and Methods:
Promoter fragments from either hTERT or hTR were used to drive the expression of NIS in cell lines derived from melanoma (M14), breast (MDA-MB-231), colon (HT-29), lung (H460), ovarian (OVCAR-3), and thyroid (TPC-1) carcinomas. Iodide uptake assays, protein immunodetection, and clonigenic assays were used to confirm NIS functional expression and the 131I-mediated cytopathic effect. Tumor xenografts in mice were infected with hTERT and hTR and then treated using radioiodide.
Results:
Both promoters were selectively active in cancer cells that were effectively killed by exposure to 131I. One single dose of 1 mCi 131I markedly suppressed tumor growth of melanoma-derived tumor xenografts compared with controls. This effect was more modest in colon cancer-derived xenografts in part due to the reduced infectivity and the tumor cystic nature. The therapeutic effect of hTR promoter was found to be stronger than that of hTERT promoter.
Conclusions:
These results demonstrate that telomerase-driven expression of NIS could potentially have applications for 131I therapy of a wide variety of cancers. Additionally, this is the first study to report NIS-mediated 131I therapy of melanoma tumors in vivo.</description><subject>Animal models</subject><subject>Animals</subject><subject>Cell Line, Tumor</subject><subject>Genetic Therapy - methods</subject><subject>Humans</subject><subject>Iodine Radioisotopes - therapeutic use</subject><subject>Mice</subject><subject>Neoplasm Transplantation</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - radiotherapy</subject><subject>Promoter Regions, Genetic</subject><subject>Symporters - genetics</subject><subject>Symporters - metabolism</subject><subject>Telomerase - genetics</subject><subject>Telomerase - metabolism</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNp9kcFu1DAQhiMEokvhxhn5RpFw8ThxEve2LAVWKkViF8TNcpyJ1ksSBzvp0ufhRfGSwglhyRqN9c1ny3-SPAV2DhzYq7055wwY5WmR3ksWIDNBC5DF_WTBGAcqC_71JHkUwp4xyDKRPkxOOOTxWKSL5OcWW9eh1wHpG29vsCeXPwaPIVjXE9eQcYdk42o7dWQdSx27225wfkRPzq7XmxekcZ7YnnyxN4580rV1dua2HvXYYT8eNSvdG_QXZEmu8UBee6druhnQjD6Ko4Z-wNrqEWuy7Ec7Tl2ULochcmb3OHnQ6Dbgk7t6mnx-e7ldvadXH9-tV8srajLBcsrBcFllTZ03mmei4o0wkEPeVCBTnlcFYApaY5nxIkubstKylNgYKWpZGqjS0-T57I3Xfp8wjKqzwWDb6h7dFFRZlkyCkCKSZ_8lgXOANANRRvTljBrvQvDYqMHbTvtbBUwdA1R7o44BqmOAEX92Z56qDuu_8J_EIpDNwMG1MYPwrZ0O6NUOdTvuFIsry4uSRiMwGTsat8jjWDqPYV87422Pv0NWezf5Pn7qv1_zC_zTt0I</recordid><startdate>201109</startdate><enddate>201109</enddate><creator>Riesco-Eizaguirre, Garcilaso</creator><creator>De la Vieja, Antonio</creator><creator>Rodríguez, Irene</creator><creator>Miranda, Soledad</creator><creator>Martín-Duque, Pilar</creator><creator>Vassaux, Georges</creator><creator>Santisteban, Pilar</creator><general>Endocrine Society</general><general>Copyright by The Endocrine Society</general><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>201109</creationdate><title>Telomerase-Driven Expression of the Sodium Iodide Symporter (NIS) for in Vivo Radioiodide Treatment of Cancer: A New Broad-Spectrum NIS-Mediated Antitumor Approach</title><author>Riesco-Eizaguirre, Garcilaso ; De la Vieja, Antonio ; Rodríguez, Irene ; Miranda, Soledad ; Martín-Duque, Pilar ; Vassaux, Georges ; Santisteban, Pilar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4506-21c29b4fd6fa245b2f5c1616fb19326b71e31aae842743f8ba989efc95d98c1b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Cell Line, Tumor</topic><topic>Genetic Therapy - methods</topic><topic>Humans</topic><topic>Iodine Radioisotopes - therapeutic use</topic><topic>Mice</topic><topic>Neoplasm Transplantation</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - metabolism</topic><topic>Neoplasms - radiotherapy</topic><topic>Promoter Regions, Genetic</topic><topic>Symporters - genetics</topic><topic>Symporters - metabolism</topic><topic>Telomerase - genetics</topic><topic>Telomerase - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Riesco-Eizaguirre, Garcilaso</creatorcontrib><creatorcontrib>De la Vieja, Antonio</creatorcontrib><creatorcontrib>Rodríguez, Irene</creatorcontrib><creatorcontrib>Miranda, Soledad</creatorcontrib><creatorcontrib>Martín-Duque, Pilar</creatorcontrib><creatorcontrib>Vassaux, Georges</creatorcontrib><creatorcontrib>Santisteban, Pilar</creatorcontrib><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>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Riesco-Eizaguirre, Garcilaso</au><au>De la Vieja, Antonio</au><au>Rodríguez, Irene</au><au>Miranda, Soledad</au><au>Martín-Duque, Pilar</au><au>Vassaux, Georges</au><au>Santisteban, Pilar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Telomerase-Driven Expression of the Sodium Iodide Symporter (NIS) for in Vivo Radioiodide Treatment of Cancer: A New Broad-Spectrum NIS-Mediated Antitumor Approach</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2011-09</date><risdate>2011</risdate><volume>96</volume><issue>9</issue><spage>E1435</spage><epage>E1443</epage><pages>E1435-E1443</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><abstract>Context:
Telomerase promoters (hTERT and hTR) are useful for transcriptional targeting in gene therapy models of cancer. Telomerase-driven expression of the sodium iodide symporter (NIS) in tumor cells has been successfully used as a reporter gene in vivo using positron emission tomography (PET) imaging.
Objective:
The aim of this study was to investigate the NIS-mediated therapeutic effect of telomerase promoters in a wide variety of human cancer cell lines.
Design and Methods:
Promoter fragments from either hTERT or hTR were used to drive the expression of NIS in cell lines derived from melanoma (M14), breast (MDA-MB-231), colon (HT-29), lung (H460), ovarian (OVCAR-3), and thyroid (TPC-1) carcinomas. Iodide uptake assays, protein immunodetection, and clonigenic assays were used to confirm NIS functional expression and the 131I-mediated cytopathic effect. Tumor xenografts in mice were infected with hTERT and hTR and then treated using radioiodide.
Results:
Both promoters were selectively active in cancer cells that were effectively killed by exposure to 131I. One single dose of 1 mCi 131I markedly suppressed tumor growth of melanoma-derived tumor xenografts compared with controls. This effect was more modest in colon cancer-derived xenografts in part due to the reduced infectivity and the tumor cystic nature. The therapeutic effect of hTR promoter was found to be stronger than that of hTERT promoter.
Conclusions:
These results demonstrate that telomerase-driven expression of NIS could potentially have applications for 131I therapy of a wide variety of cancers. Additionally, this is the first study to report NIS-mediated 131I therapy of melanoma tumors in vivo.</abstract><cop>United States</cop><pub>Endocrine Society</pub><pmid>21697253</pmid><doi>10.1210/jc.2010-2373</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-972X |
| ispartof | The journal of clinical endocrinology and metabolism, 2011-09, Vol.96 (9), p.E1435-E1443 |
| issn | 0021-972X 1945-7197 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_888091595 |
| source | Oxford Journals Online |
| subjects | Animal models Animals Cell Line, Tumor Genetic Therapy - methods Humans Iodine Radioisotopes - therapeutic use Mice Neoplasm Transplantation Neoplasms - genetics Neoplasms - metabolism Neoplasms - radiotherapy Promoter Regions, Genetic Symporters - genetics Symporters - metabolism Telomerase - genetics Telomerase - metabolism |
| title | Telomerase-Driven Expression of the Sodium Iodide Symporter (NIS) for in Vivo Radioiodide Treatment of Cancer: A New Broad-Spectrum NIS-Mediated Antitumor Approach |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T12%3A36%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Telomerase-Driven%20Expression%20of%20the%20Sodium%20Iodide%20Symporter%20(NIS)%20for%20in%20Vivo%20Radioiodide%20Treatment%20of%20Cancer:%20A%20New%20Broad-Spectrum%20NIS-Mediated%20Antitumor%20Approach&rft.jtitle=The%20journal%20of%20clinical%20endocrinology%20and%20metabolism&rft.au=Riesco-Eizaguirre,%20Garcilaso&rft.date=2011-09&rft.volume=96&rft.issue=9&rft.spage=E1435&rft.epage=E1443&rft.pages=E1435-E1443&rft.issn=0021-972X&rft.eissn=1945-7197&rft_id=info:doi/10.1210/jc.2010-2373&rft_dat=%3Cproquest_cross%3E1221134158%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c4506-21c29b4fd6fa245b2f5c1616fb19326b71e31aae842743f8ba989efc95d98c1b3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1221134158&rft_id=info:pmid/21697253&rfr_iscdi=true |