Cross-resistance to the synthetic retinoid CD437 in a paclitaxel-resistant human ovarian carcinoma cell line is independent of the overexpression of retinoic acid receptor-γ
Treatment of ovarian carcinomas with the antimitotic antitumor drug paclitaxel is highly efficacious. However, development of drug resistance presents a major obstacle. The common cellular phenotypes associated with paclitaxel resistance are an increased expression of the drug transport protein P-gl...
Gespeichert in:
| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2001-10, Vol.61 (20), p.7552-7555 |
|---|---|
| Hauptverfasser: | , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 7555 |
|---|---|
| container_issue | 20 |
| container_start_page | 7552 |
| container_title | Cancer research (Chicago, Ill.) |
| container_volume | 61 |
| creator | KUMAR, Atul SOPRANO, Dianne R PAREKH, Hemant K |
| description | Treatment of ovarian carcinomas with the antimitotic antitumor drug paclitaxel is highly efficacious. However, development of drug resistance presents a major obstacle. The common cellular phenotypes associated with paclitaxel resistance are an increased expression of the drug transport protein P-glycoprotein (P-gp), an alteration in the levels of beta-tubulin isotypes, and/or changes in the drug binding affinity of the microtubules. We established two paclitaxel-resistant human ovarian carcinoma cell lines. The 2008/17/4 cells exhibited a "classic" multidrug-resistant phenotype (overexpression of P-gp associated with cross-resistance to natural product drugs), whereas the 2008/13/4 cells were an atypical multidrug-resistant subline (no overexpression of P-gp). In addition to being paclitaxel resistant (250-fold), the 2008/13/4 cells were also cross-resistant to etoposide (39-fold) and vincristine (460-fold). To identify the alterations in the gene expression profile associated with the development of atypical paclitaxel resistance, we used the Clontech Atlas Human Cancer cDNA Microarray (spotted with 588 genes). The expression of retinoic acid receptor (RAR)-gamma was significantly higher in the paclitaxel-resistant (2008/13/4 and 2008/17/4) cells than in the parental (2008) cells. Northern blotting analysis demonstrated that the expression of RAR-gamma was 7-fold higher in the 2008/13/4 and 2008/17/4 cells than in the 2008 cells, whereas the expression of RAR-alpha and RAR-beta was not observed in any cell line. Whereas the 2008, 2008/13/4, and 2008/17/4 cells were found to resist the antiproliferative effects of all-trans-retinoic acid, the paclitaxel-resistant cells were 6- to 7-fold cross-resistant to the antiproliferative effects of CD437 (a synthetic RAR-gamma-selective agonist; 6-[-(1-admantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid) compared with the sensitivity of the parental cells. To further understand the association of paclitaxel and CD437 resistance with the observed RAR-gamma overexpression, we transfected the 2008 cells with a full-length RAR-gamma cDNA construct. Two transfectants with increased expression of the RAR-gamma mRNA and protein were isolated and subjected to growth inhibition assays in the presence of various concentrations of paclitaxel, etoposide, vincristine, and CD437. The sensitivity of the 2008 transfected clones (displaying increased expression of RAR-gamma) to the cytotoxic effects of paclitaxel, etoposide, vin |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_72206797</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>72206797</sourcerecordid><originalsourceid>FETCH-LOGICAL-p237t-63f1fa86c1d516cb7e1cc7262004ae4ca650dd5d7899ff07d515a6145adc93543</originalsourceid><addsrcrecordid>eNpFkE1OwzAQhSMEoqVwBeQN7CLZ8V-yROFXqsQG1tXUmahGSRxstyqXYsM9OBMuFNjM04y-N08zB9mUSV7mWgh5mE0ppWUuhS4m2UkIL6mVjMrjbMKYoopXfJq9196FkHsMNkQYDJLoSFwhCW9DkmgN8akOzjakvhZcEzsQICOYzkbYYvdnjWS17mEgbgPeJjXgTfL1QAx2HensgMSGZG9wxFSSwbXfUW6DHrdjWhSsG3bTfaQhYFKuR4NjdD7__DjNjlroAp7tdZY939481ff5_PHuob6a52PBdcwVb1kLpTKskUyZpUZmjC5UQakAFAaUpE0jG11WVdtSnSgJigkJjam4FHyWXf7sHb17XWOIi96G3R0woFuHhS4KqnSlE3i-B9fLHpvF6G0P_m3x--EEXOwBCAa61qcn2_DPCUY1k4p_ASWLidM</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>72206797</pqid></control><display><type>article</type><title>Cross-resistance to the synthetic retinoid CD437 in a paclitaxel-resistant human ovarian carcinoma cell line is independent of the overexpression of retinoic acid receptor-γ</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>KUMAR, Atul ; SOPRANO, Dianne R ; PAREKH, Hemant K</creator><creatorcontrib>KUMAR, Atul ; SOPRANO, Dianne R ; PAREKH, Hemant K</creatorcontrib><description>Treatment of ovarian carcinomas with the antimitotic antitumor drug paclitaxel is highly efficacious. However, development of drug resistance presents a major obstacle. The common cellular phenotypes associated with paclitaxel resistance are an increased expression of the drug transport protein P-glycoprotein (P-gp), an alteration in the levels of beta-tubulin isotypes, and/or changes in the drug binding affinity of the microtubules. We established two paclitaxel-resistant human ovarian carcinoma cell lines. The 2008/17/4 cells exhibited a "classic" multidrug-resistant phenotype (overexpression of P-gp associated with cross-resistance to natural product drugs), whereas the 2008/13/4 cells were an atypical multidrug-resistant subline (no overexpression of P-gp). In addition to being paclitaxel resistant (250-fold), the 2008/13/4 cells were also cross-resistant to etoposide (39-fold) and vincristine (460-fold). To identify the alterations in the gene expression profile associated with the development of atypical paclitaxel resistance, we used the Clontech Atlas Human Cancer cDNA Microarray (spotted with 588 genes). The expression of retinoic acid receptor (RAR)-gamma was significantly higher in the paclitaxel-resistant (2008/13/4 and 2008/17/4) cells than in the parental (2008) cells. Northern blotting analysis demonstrated that the expression of RAR-gamma was 7-fold higher in the 2008/13/4 and 2008/17/4 cells than in the 2008 cells, whereas the expression of RAR-alpha and RAR-beta was not observed in any cell line. Whereas the 2008, 2008/13/4, and 2008/17/4 cells were found to resist the antiproliferative effects of all-trans-retinoic acid, the paclitaxel-resistant cells were 6- to 7-fold cross-resistant to the antiproliferative effects of CD437 (a synthetic RAR-gamma-selective agonist; 6-[-(1-admantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid) compared with the sensitivity of the parental cells. To further understand the association of paclitaxel and CD437 resistance with the observed RAR-gamma overexpression, we transfected the 2008 cells with a full-length RAR-gamma cDNA construct. Two transfectants with increased expression of the RAR-gamma mRNA and protein were isolated and subjected to growth inhibition assays in the presence of various concentrations of paclitaxel, etoposide, vincristine, and CD437. The sensitivity of the 2008 transfected clones (displaying increased expression of RAR-gamma) to the cytotoxic effects of paclitaxel, etoposide, vincristine, and CD437 was similar to that observed in the parental 2008 cells. These results suggest that the overexpression of RAR-gamma (observed in the 2008/13/4 and 2008/17/4 cells) by itself is not capable of inducing paclitaxel and CD437 resistance (or resistance to etoposide and vincristine).</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>PMID: 11606393</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Antineoplastic agents ; Antineoplastic Agents - pharmacology ; Biological and medical sciences ; Blotting, Northern ; Chemotherapy ; Drug Resistance, Multiple - genetics ; Drug Resistance, Multiple - physiology ; Drug Resistance, Neoplasm ; Female ; Humans ; Medical sciences ; Oligonucleotide Array Sequence Analysis ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - metabolism ; Paclitaxel - pharmacology ; Pharmacology. Drug treatments ; Receptors, Retinoic Acid - biosynthesis ; Receptors, Retinoic Acid - genetics ; Retinoic Acid Receptor gamma ; Retinoids - pharmacology ; Tumor Cells, Cultured - drug effects</subject><ispartof>Cancer research (Chicago, Ill.), 2001-10, Vol.61 (20), p.7552-7555</ispartof><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14107156$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11606393$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KUMAR, Atul</creatorcontrib><creatorcontrib>SOPRANO, Dianne R</creatorcontrib><creatorcontrib>PAREKH, Hemant K</creatorcontrib><title>Cross-resistance to the synthetic retinoid CD437 in a paclitaxel-resistant human ovarian carcinoma cell line is independent of the overexpression of retinoic acid receptor-γ</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>Treatment of ovarian carcinomas with the antimitotic antitumor drug paclitaxel is highly efficacious. However, development of drug resistance presents a major obstacle. The common cellular phenotypes associated with paclitaxel resistance are an increased expression of the drug transport protein P-glycoprotein (P-gp), an alteration in the levels of beta-tubulin isotypes, and/or changes in the drug binding affinity of the microtubules. We established two paclitaxel-resistant human ovarian carcinoma cell lines. The 2008/17/4 cells exhibited a "classic" multidrug-resistant phenotype (overexpression of P-gp associated with cross-resistance to natural product drugs), whereas the 2008/13/4 cells were an atypical multidrug-resistant subline (no overexpression of P-gp). In addition to being paclitaxel resistant (250-fold), the 2008/13/4 cells were also cross-resistant to etoposide (39-fold) and vincristine (460-fold). To identify the alterations in the gene expression profile associated with the development of atypical paclitaxel resistance, we used the Clontech Atlas Human Cancer cDNA Microarray (spotted with 588 genes). The expression of retinoic acid receptor (RAR)-gamma was significantly higher in the paclitaxel-resistant (2008/13/4 and 2008/17/4) cells than in the parental (2008) cells. Northern blotting analysis demonstrated that the expression of RAR-gamma was 7-fold higher in the 2008/13/4 and 2008/17/4 cells than in the 2008 cells, whereas the expression of RAR-alpha and RAR-beta was not observed in any cell line. Whereas the 2008, 2008/13/4, and 2008/17/4 cells were found to resist the antiproliferative effects of all-trans-retinoic acid, the paclitaxel-resistant cells were 6- to 7-fold cross-resistant to the antiproliferative effects of CD437 (a synthetic RAR-gamma-selective agonist; 6-[-(1-admantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid) compared with the sensitivity of the parental cells. To further understand the association of paclitaxel and CD437 resistance with the observed RAR-gamma overexpression, we transfected the 2008 cells with a full-length RAR-gamma cDNA construct. Two transfectants with increased expression of the RAR-gamma mRNA and protein were isolated and subjected to growth inhibition assays in the presence of various concentrations of paclitaxel, etoposide, vincristine, and CD437. The sensitivity of the 2008 transfected clones (displaying increased expression of RAR-gamma) to the cytotoxic effects of paclitaxel, etoposide, vincristine, and CD437 was similar to that observed in the parental 2008 cells. These results suggest that the overexpression of RAR-gamma (observed in the 2008/13/4 and 2008/17/4 cells) by itself is not capable of inducing paclitaxel and CD437 resistance (or resistance to etoposide and vincristine).</description><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Blotting, Northern</subject><subject>Chemotherapy</subject><subject>Drug Resistance, Multiple - genetics</subject><subject>Drug Resistance, Multiple - physiology</subject><subject>Drug Resistance, Neoplasm</subject><subject>Female</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Paclitaxel - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Receptors, Retinoic Acid - biosynthesis</subject><subject>Receptors, Retinoic Acid - genetics</subject><subject>Retinoic Acid Receptor gamma</subject><subject>Retinoids - pharmacology</subject><subject>Tumor Cells, Cultured - drug effects</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1OwzAQhSMEoqVwBeQN7CLZ8V-yROFXqsQG1tXUmahGSRxstyqXYsM9OBMuFNjM04y-N08zB9mUSV7mWgh5mE0ppWUuhS4m2UkIL6mVjMrjbMKYoopXfJq9196FkHsMNkQYDJLoSFwhCW9DkmgN8akOzjakvhZcEzsQICOYzkbYYvdnjWS17mEgbgPeJjXgTfL1QAx2HensgMSGZG9wxFSSwbXfUW6DHrdjWhSsG3bTfaQhYFKuR4NjdD7__DjNjlroAp7tdZY939481ff5_PHuob6a52PBdcwVb1kLpTKskUyZpUZmjC5UQakAFAaUpE0jG11WVdtSnSgJigkJjam4FHyWXf7sHb17XWOIi96G3R0woFuHhS4KqnSlE3i-B9fLHpvF6G0P_m3x--EEXOwBCAa61qcn2_DPCUY1k4p_ASWLidM</recordid><startdate>20011015</startdate><enddate>20011015</enddate><creator>KUMAR, Atul</creator><creator>SOPRANO, Dianne R</creator><creator>PAREKH, Hemant K</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20011015</creationdate><title>Cross-resistance to the synthetic retinoid CD437 in a paclitaxel-resistant human ovarian carcinoma cell line is independent of the overexpression of retinoic acid receptor-γ</title><author>KUMAR, Atul ; SOPRANO, Dianne R ; PAREKH, Hemant K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p237t-63f1fa86c1d516cb7e1cc7262004ae4ca650dd5d7899ff07d515a6145adc93543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Blotting, Northern</topic><topic>Chemotherapy</topic><topic>Drug Resistance, Multiple - genetics</topic><topic>Drug Resistance, Multiple - physiology</topic><topic>Drug Resistance, Neoplasm</topic><topic>Female</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - metabolism</topic><topic>Paclitaxel - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Receptors, Retinoic Acid - biosynthesis</topic><topic>Receptors, Retinoic Acid - genetics</topic><topic>Retinoic Acid Receptor gamma</topic><topic>Retinoids - pharmacology</topic><topic>Tumor Cells, Cultured - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KUMAR, Atul</creatorcontrib><creatorcontrib>SOPRANO, Dianne R</creatorcontrib><creatorcontrib>PAREKH, Hemant K</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>MEDLINE - Academic</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KUMAR, Atul</au><au>SOPRANO, Dianne R</au><au>PAREKH, Hemant K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cross-resistance to the synthetic retinoid CD437 in a paclitaxel-resistant human ovarian carcinoma cell line is independent of the overexpression of retinoic acid receptor-γ</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2001-10-15</date><risdate>2001</risdate><volume>61</volume><issue>20</issue><spage>7552</spage><epage>7555</epage><pages>7552-7555</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>Treatment of ovarian carcinomas with the antimitotic antitumor drug paclitaxel is highly efficacious. However, development of drug resistance presents a major obstacle. The common cellular phenotypes associated with paclitaxel resistance are an increased expression of the drug transport protein P-glycoprotein (P-gp), an alteration in the levels of beta-tubulin isotypes, and/or changes in the drug binding affinity of the microtubules. We established two paclitaxel-resistant human ovarian carcinoma cell lines. The 2008/17/4 cells exhibited a "classic" multidrug-resistant phenotype (overexpression of P-gp associated with cross-resistance to natural product drugs), whereas the 2008/13/4 cells were an atypical multidrug-resistant subline (no overexpression of P-gp). In addition to being paclitaxel resistant (250-fold), the 2008/13/4 cells were also cross-resistant to etoposide (39-fold) and vincristine (460-fold). To identify the alterations in the gene expression profile associated with the development of atypical paclitaxel resistance, we used the Clontech Atlas Human Cancer cDNA Microarray (spotted with 588 genes). The expression of retinoic acid receptor (RAR)-gamma was significantly higher in the paclitaxel-resistant (2008/13/4 and 2008/17/4) cells than in the parental (2008) cells. Northern blotting analysis demonstrated that the expression of RAR-gamma was 7-fold higher in the 2008/13/4 and 2008/17/4 cells than in the 2008 cells, whereas the expression of RAR-alpha and RAR-beta was not observed in any cell line. Whereas the 2008, 2008/13/4, and 2008/17/4 cells were found to resist the antiproliferative effects of all-trans-retinoic acid, the paclitaxel-resistant cells were 6- to 7-fold cross-resistant to the antiproliferative effects of CD437 (a synthetic RAR-gamma-selective agonist; 6-[-(1-admantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid) compared with the sensitivity of the parental cells. To further understand the association of paclitaxel and CD437 resistance with the observed RAR-gamma overexpression, we transfected the 2008 cells with a full-length RAR-gamma cDNA construct. Two transfectants with increased expression of the RAR-gamma mRNA and protein were isolated and subjected to growth inhibition assays in the presence of various concentrations of paclitaxel, etoposide, vincristine, and CD437. The sensitivity of the 2008 transfected clones (displaying increased expression of RAR-gamma) to the cytotoxic effects of paclitaxel, etoposide, vincristine, and CD437 was similar to that observed in the parental 2008 cells. These results suggest that the overexpression of RAR-gamma (observed in the 2008/13/4 and 2008/17/4 cells) by itself is not capable of inducing paclitaxel and CD437 resistance (or resistance to etoposide and vincristine).</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>11606393</pmid><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0008-5472 |
| ispartof | Cancer research (Chicago, Ill.), 2001-10, Vol.61 (20), p.7552-7555 |
| issn | 0008-5472 1538-7445 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_72206797 |
| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals |
| subjects | Antineoplastic agents Antineoplastic Agents - pharmacology Biological and medical sciences Blotting, Northern Chemotherapy Drug Resistance, Multiple - genetics Drug Resistance, Multiple - physiology Drug Resistance, Neoplasm Female Humans Medical sciences Oligonucleotide Array Sequence Analysis Ovarian Neoplasms - drug therapy Ovarian Neoplasms - genetics Ovarian Neoplasms - metabolism Paclitaxel - pharmacology Pharmacology. Drug treatments Receptors, Retinoic Acid - biosynthesis Receptors, Retinoic Acid - genetics Retinoic Acid Receptor gamma Retinoids - pharmacology Tumor Cells, Cultured - drug effects |
| title | Cross-resistance to the synthetic retinoid CD437 in a paclitaxel-resistant human ovarian carcinoma cell line is independent of the overexpression of retinoic acid receptor-γ |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-10T20%3A56%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cross-resistance%20to%20the%20synthetic%20retinoid%20CD437%20in%20a%20paclitaxel-resistant%20human%20ovarian%20carcinoma%20cell%20line%20is%20independent%20of%20the%20overexpression%20of%20retinoic%20acid%20receptor-%CE%B3&rft.jtitle=Cancer%20research%20(Chicago,%20Ill.)&rft.au=KUMAR,%20Atul&rft.date=2001-10-15&rft.volume=61&rft.issue=20&rft.spage=7552&rft.epage=7555&rft.pages=7552-7555&rft.issn=0008-5472&rft.eissn=1538-7445&rft.coden=CNREA8&rft_id=info:doi/&rft_dat=%3Cproquest_pubme%3E72206797%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=72206797&rft_id=info:pmid/11606393&rfr_iscdi=true |