Gene expression and pathway analysis of ovarian cancer cells selected for resistance to cisplatin, paclitaxel, or doxorubicin
<p>Abstract</p> <p>Background</p> <p>Resistance to current chemotherapeutic agents is a major cause of therapy failure in ovarian cancer patients, but the exact mechanisms leading to the development of drug resistance remain unclear.</p> <p>Methods</p>...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-12-01
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| Series: | Journal of Ovarian Research |
| Online Access: | http://www.ovarianresearch.com/content/4/1/21 |
| _version_ | 1797970367159992320 |
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| author | Sherman-Baust Cheryl A Becker Kevin G Wood III William H Zhang Yongqing Morin Patrice J |
| author_facet | Sherman-Baust Cheryl A Becker Kevin G Wood III William H Zhang Yongqing Morin Patrice J |
| author_sort | Sherman-Baust Cheryl A |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Resistance to current chemotherapeutic agents is a major cause of therapy failure in ovarian cancer patients, but the exact mechanisms leading to the development of drug resistance remain unclear.</p> <p>Methods</p> <p>To better understand mechanisms of drug resistance, and possibly identify novel targets for therapy, we generated a series of drug resistant ovarian cancer cell lines through repeated exposure to three chemotherapeutic drugs (cisplatin, doxorubicin, or paclitaxel), and identified changes in gene expression patterns using Illumina whole-genome expression microarrays. Validation of selected genes was performed by RT-PCR and immunoblotting. Pathway enrichment analysis using the KEGG, GO, and Reactome databases was performed to identify pathways that may be important in each drug resistance phenotype.</p> <p>Results</p> <p>A total of 845 genes (p < 0.01) were found altered in at least one drug resistance phenotype when compared to the parental, drug sensitive cell line. Focusing on each resistance phenotype individually, we identified 460, 366, and 337 genes significantly altered in cells resistant to cisplatin, doxorubicin, and paclitaxel, respectively. Of the 845 genes found altered, only 62 genes were simultaneously altered in all three resistance phenotypes. Using pathway analysis, we found many pathways enriched for each resistance phenotype, but some dominant pathways emerged. The dominant pathways included signaling from the cell surface and cell movement for cisplatin resistance, proteasome regulation and steroid biosynthesis for doxorubicin resistance, and control of translation and oxidative stress for paclitaxel resistance.</p> <p>Conclusions</p> <p>Ovarian cancer cells develop drug resistance through different pathways depending on the drug used in the generation of chemoresistance. A better understanding of these mechanisms may lead to the development of novel strategies to circumvent the problem of drug resistance.</p> |
| first_indexed | 2024-04-11T03:16:48Z |
| format | Article |
| id | doaj.art-1bc81628d0f340639f680af3305b19d4 |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-04-11T03:16:48Z |
| publishDate | 2011-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-1bc81628d0f340639f680af3305b19d42023-01-02T10:10:21ZengBMCJournal of Ovarian Research1757-22152011-12-01412110.1186/1757-2215-4-21Gene expression and pathway analysis of ovarian cancer cells selected for resistance to cisplatin, paclitaxel, or doxorubicinSherman-Baust Cheryl ABecker Kevin GWood III William HZhang YongqingMorin Patrice J<p>Abstract</p> <p>Background</p> <p>Resistance to current chemotherapeutic agents is a major cause of therapy failure in ovarian cancer patients, but the exact mechanisms leading to the development of drug resistance remain unclear.</p> <p>Methods</p> <p>To better understand mechanisms of drug resistance, and possibly identify novel targets for therapy, we generated a series of drug resistant ovarian cancer cell lines through repeated exposure to three chemotherapeutic drugs (cisplatin, doxorubicin, or paclitaxel), and identified changes in gene expression patterns using Illumina whole-genome expression microarrays. Validation of selected genes was performed by RT-PCR and immunoblotting. Pathway enrichment analysis using the KEGG, GO, and Reactome databases was performed to identify pathways that may be important in each drug resistance phenotype.</p> <p>Results</p> <p>A total of 845 genes (p < 0.01) were found altered in at least one drug resistance phenotype when compared to the parental, drug sensitive cell line. Focusing on each resistance phenotype individually, we identified 460, 366, and 337 genes significantly altered in cells resistant to cisplatin, doxorubicin, and paclitaxel, respectively. Of the 845 genes found altered, only 62 genes were simultaneously altered in all three resistance phenotypes. Using pathway analysis, we found many pathways enriched for each resistance phenotype, but some dominant pathways emerged. The dominant pathways included signaling from the cell surface and cell movement for cisplatin resistance, proteasome regulation and steroid biosynthesis for doxorubicin resistance, and control of translation and oxidative stress for paclitaxel resistance.</p> <p>Conclusions</p> <p>Ovarian cancer cells develop drug resistance through different pathways depending on the drug used in the generation of chemoresistance. A better understanding of these mechanisms may lead to the development of novel strategies to circumvent the problem of drug resistance.</p>http://www.ovarianresearch.com/content/4/1/21 |
| spellingShingle | Sherman-Baust Cheryl A Becker Kevin G Wood III William H Zhang Yongqing Morin Patrice J Gene expression and pathway analysis of ovarian cancer cells selected for resistance to cisplatin, paclitaxel, or doxorubicin Journal of Ovarian Research |
| title | Gene expression and pathway analysis of ovarian cancer cells selected for resistance to cisplatin, paclitaxel, or doxorubicin |
| title_full | Gene expression and pathway analysis of ovarian cancer cells selected for resistance to cisplatin, paclitaxel, or doxorubicin |
| title_fullStr | Gene expression and pathway analysis of ovarian cancer cells selected for resistance to cisplatin, paclitaxel, or doxorubicin |
| title_full_unstemmed | Gene expression and pathway analysis of ovarian cancer cells selected for resistance to cisplatin, paclitaxel, or doxorubicin |
| title_short | Gene expression and pathway analysis of ovarian cancer cells selected for resistance to cisplatin, paclitaxel, or doxorubicin |
| title_sort | gene expression and pathway analysis of ovarian cancer cells selected for resistance to cisplatin paclitaxel or doxorubicin |
| url | http://www.ovarianresearch.com/content/4/1/21 |
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