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Conference Paper: MAD2 expression induces chemosensitization to DNA damaging agent, cisplatin, in nasopharyngeal carcinoma cells
Title | MAD2 expression induces chemosensitization to DNA damaging agent, cisplatin, in nasopharyngeal carcinoma cells |
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Authors | |
Issue Date | 2005 |
Publisher | American Association for Cancer Research. |
Citation | The 96th Annual Meeting of the American Association for Cancer Research (AACR 2005), Anaheim CA., 16–20 April 2005. In Cancer Research, 2005, v. 65 n. 9S, p. 1259, abstract no. 5326 How to Cite? |
Abstract | Recently, MAD2 (mitotic arrest deficient 2)-mediated spindle checkpoint is shown to induce mitotic arrest in response to DNA damage, indicating overlapping roles of the spindle checkpoint and DNA damage checkpoint. In this study, we investigated if MAD2 played a part in cellular sensitivity to DNA damaging agents, especially cisplatin, and whether it was regulated through mitotic checkpoint. Using nine nasopharyngeal carcinoma (NPC) cell lines, we found that decreased MAD2 expression was correlated with cellular resistance to cisplatin compared to the cell lines with high levels of MAD2. Exogenous MAD2 expression in NPC cells also conferred sensitivity to DNA damaging agents especially cisplatin but not other anticancer drugs with different mechanisms of action. The increased cisplatin sensitivity in MAD2 transfectants was associated with mitotic arrest and activation of apoptosis pathway evidenced by the increased mitotic index and apoptosis rate as well as decreased Bcl-2 to Bax ratio and expression of cleaved PARP and Caspase 3. Our results indicate that the MAD2-induced chemosensitization to cisplatin in NPC cells is mediated through the induction of mitotic arrest which in turn activates the apoptosis pathway. Our evidence further confirms previous hypothesis that spindle checkpoint plays an important part in DNA damage-induced cell cycle arrest and suggests a novel role of MAD2 in cellular sensitivity to cisplatin. |
Persistent Identifier | http://hdl.handle.net/10722/95167 |
ISSN | 2023 Impact Factor: 12.5 2023 SCImago Journal Rankings: 3.468 |
DC Field | Value | Language |
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dc.contributor.author | Cheung, HW | en_HK |
dc.contributor.author | Jin, D | en_HK |
dc.contributor.author | Ling, MT | en_HK |
dc.contributor.author | Wong, YC | en_HK |
dc.contributor.author | Wang, Q | en_HK |
dc.contributor.author | Tsao, GSW | en_HK |
dc.contributor.author | Wang, X | en_HK |
dc.date.accessioned | 2010-09-25T15:53:44Z | - |
dc.date.available | 2010-09-25T15:53:44Z | - |
dc.date.issued | 2005 | en_HK |
dc.identifier.citation | The 96th Annual Meeting of the American Association for Cancer Research (AACR 2005), Anaheim CA., 16–20 April 2005. In Cancer Research, 2005, v. 65 n. 9S, p. 1259, abstract no. 5326 | en_HK |
dc.identifier.issn | 0008-5472 | - |
dc.identifier.uri | http://hdl.handle.net/10722/95167 | - |
dc.description.abstract | Recently, MAD2 (mitotic arrest deficient 2)-mediated spindle checkpoint is shown to induce mitotic arrest in response to DNA damage, indicating overlapping roles of the spindle checkpoint and DNA damage checkpoint. In this study, we investigated if MAD2 played a part in cellular sensitivity to DNA damaging agents, especially cisplatin, and whether it was regulated through mitotic checkpoint. Using nine nasopharyngeal carcinoma (NPC) cell lines, we found that decreased MAD2 expression was correlated with cellular resistance to cisplatin compared to the cell lines with high levels of MAD2. Exogenous MAD2 expression in NPC cells also conferred sensitivity to DNA damaging agents especially cisplatin but not other anticancer drugs with different mechanisms of action. The increased cisplatin sensitivity in MAD2 transfectants was associated with mitotic arrest and activation of apoptosis pathway evidenced by the increased mitotic index and apoptosis rate as well as decreased Bcl-2 to Bax ratio and expression of cleaved PARP and Caspase 3. Our results indicate that the MAD2-induced chemosensitization to cisplatin in NPC cells is mediated through the induction of mitotic arrest which in turn activates the apoptosis pathway. Our evidence further confirms previous hypothesis that spindle checkpoint plays an important part in DNA damage-induced cell cycle arrest and suggests a novel role of MAD2 in cellular sensitivity to cisplatin. | - |
dc.language | eng | en_HK |
dc.publisher | American Association for Cancer Research. | - |
dc.relation.ispartof | Cancer Research | en_HK |
dc.title | MAD2 expression induces chemosensitization to DNA damaging agent, cisplatin, in nasopharyngeal carcinoma cells | en_HK |
dc.type | Conference_Paper | en_HK |
dc.identifier.email | Jin, D: dyjin@hkucc.hku.hk | en_HK |
dc.identifier.email | Ling, MT: patling@HKUCC.hku.hk | en_HK |
dc.identifier.email | Wong, YC: ycwong@hkucc.hku.hk | en_HK |
dc.identifier.email | Wang, Q: wangqi168@yahoo.com | en_HK |
dc.identifier.email | Tsao, GSW: gswtsao@hkucc.hku.hk | en_HK |
dc.identifier.authority | Jin, D=rp00452 | en_HK |
dc.identifier.authority | Ling, MT=rp00449 | en_HK |
dc.identifier.authority | Wong, YC=rp00316 | en_HK |
dc.identifier.authority | Tsao, GSW=rp00399 | en_HK |
dc.identifier.hkuros | 98010 | en_HK |
dc.identifier.volume | 65 | en_HK |
dc.identifier.issue | 9 suppl. | - |
dc.identifier.spage | 1259, abstract no. 5326 | en_HK |
dc.identifier.epage | 1259, abstract no. 5326 | - |
dc.identifier.issnl | 0008-5472 | - |