Deregulation of the spindle assembly checkpoint is associated with paclitaxel resistance in ovarian cancer
Abstract Background Ovarian cancer is the leading gynecologic cancer diagnosed in North America and because related symptoms are not disease specific, this often leads to late detection, an advanced disease state, and the need for chemotherapy. Ovarian cancer is frequently sensitive to chemotherapy...
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| Format: | Article |
| Language: | English |
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BMC
2018-04-01
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| Series: | Journal of Ovarian Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13048-018-0399-7 |
| _version_ | 1797969229478100992 |
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| author | Taryne Chong Amila Sarac Cindy Q. Yao Linda Liao Nicola Lyttle Paul C. Boutros John M. S. Bartlett Melanie Spears |
| author_facet | Taryne Chong Amila Sarac Cindy Q. Yao Linda Liao Nicola Lyttle Paul C. Boutros John M. S. Bartlett Melanie Spears |
| author_sort | Taryne Chong |
| collection | DOAJ |
| description | Abstract Background Ovarian cancer is the leading gynecologic cancer diagnosed in North America and because related symptoms are not disease specific, this often leads to late detection, an advanced disease state, and the need for chemotherapy. Ovarian cancer is frequently sensitive to chemotherapy at diagnosis but rapid development of drug resistance leads to disease progression and ultimately death in the majority of patients. Results We have generated paclitaxel resistant ovarian cell lines from their corresponding native cell lines to determine driver mechanisms of drug resistance using gene expression arrays. These paclitaxel resistant ovarian cells demonstrate: (1) Increased IC50 for paclitaxel and docetaxel (10 to 75-fold) and cross-resistance to anthracyclines (2) Reduced cell apoptosis in the presence of paclitaxel (3) Gene depletion involving mitotic regulators BUB1 mitotic checkpoint serine/threonine kinase, cyclin BI (CCNB1), centromere protein E (CENPE), and centromere protein F (CENPF), and (4) Functional data validating gene depletion among mitotic regulators. Conclusions We have generated model systems to explore drug resistance in ovarian cancer, which have revealed a key pathway related to the spindle assembly checkpoint underlying paclitaxel resistance in ovarian cell lines. |
| first_indexed | 2024-04-11T02:58:52Z |
| format | Article |
| id | doaj.art-d532563778fa47cdaa8d9f2b318f175c |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-04-11T02:58:52Z |
| publishDate | 2018-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-d532563778fa47cdaa8d9f2b318f175c2023-01-02T14:27:56ZengBMCJournal of Ovarian Research1757-22152018-04-011111910.1186/s13048-018-0399-7Deregulation of the spindle assembly checkpoint is associated with paclitaxel resistance in ovarian cancerTaryne Chong0Amila Sarac1Cindy Q. Yao2Linda Liao3Nicola Lyttle4Paul C. Boutros5John M. S. Bartlett6Melanie Spears7Diagnostic Development, Ontario Institute for Cancer Research, MaRS CentreDiagnostic Development, Ontario Institute for Cancer Research, MaRS CentreInformatics Program, Ontario Institute for Cancer Research, MaRS CentreDiagnostic Development, Ontario Institute for Cancer Research, MaRS CentreDiagnostic Development, Ontario Institute for Cancer Research, MaRS CentreInformatics Program, Ontario Institute for Cancer Research, MaRS CentreDiagnostic Development, Ontario Institute for Cancer Research, MaRS CentreDiagnostic Development, Ontario Institute for Cancer Research, MaRS CentreAbstract Background Ovarian cancer is the leading gynecologic cancer diagnosed in North America and because related symptoms are not disease specific, this often leads to late detection, an advanced disease state, and the need for chemotherapy. Ovarian cancer is frequently sensitive to chemotherapy at diagnosis but rapid development of drug resistance leads to disease progression and ultimately death in the majority of patients. Results We have generated paclitaxel resistant ovarian cell lines from their corresponding native cell lines to determine driver mechanisms of drug resistance using gene expression arrays. These paclitaxel resistant ovarian cells demonstrate: (1) Increased IC50 for paclitaxel and docetaxel (10 to 75-fold) and cross-resistance to anthracyclines (2) Reduced cell apoptosis in the presence of paclitaxel (3) Gene depletion involving mitotic regulators BUB1 mitotic checkpoint serine/threonine kinase, cyclin BI (CCNB1), centromere protein E (CENPE), and centromere protein F (CENPF), and (4) Functional data validating gene depletion among mitotic regulators. Conclusions We have generated model systems to explore drug resistance in ovarian cancer, which have revealed a key pathway related to the spindle assembly checkpoint underlying paclitaxel resistance in ovarian cell lines.http://link.springer.com/article/10.1186/s13048-018-0399-7Spindle assembly checkpointOvarian cancerPaclitaxelMitotic checkpoint serine/threonine kinase (BUB1)centromere protein E (CENPE)Centromere protein F (CENPF) |
| spellingShingle | Taryne Chong Amila Sarac Cindy Q. Yao Linda Liao Nicola Lyttle Paul C. Boutros John M. S. Bartlett Melanie Spears Deregulation of the spindle assembly checkpoint is associated with paclitaxel resistance in ovarian cancer Journal of Ovarian Research Spindle assembly checkpoint Ovarian cancer Paclitaxel Mitotic checkpoint serine/threonine kinase (BUB1) centromere protein E (CENPE) Centromere protein F (CENPF) |
| title | Deregulation of the spindle assembly checkpoint is associated with paclitaxel resistance in ovarian cancer |
| title_full | Deregulation of the spindle assembly checkpoint is associated with paclitaxel resistance in ovarian cancer |
| title_fullStr | Deregulation of the spindle assembly checkpoint is associated with paclitaxel resistance in ovarian cancer |
| title_full_unstemmed | Deregulation of the spindle assembly checkpoint is associated with paclitaxel resistance in ovarian cancer |
| title_short | Deregulation of the spindle assembly checkpoint is associated with paclitaxel resistance in ovarian cancer |
| title_sort | deregulation of the spindle assembly checkpoint is associated with paclitaxel resistance in ovarian cancer |
| topic | Spindle assembly checkpoint Ovarian cancer Paclitaxel Mitotic checkpoint serine/threonine kinase (BUB1) centromere protein E (CENPE) Centromere protein F (CENPF) |
| url | http://link.springer.com/article/10.1186/s13048-018-0399-7 |
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