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Conference Paper: Loss of MKP3 is associated with cisplatin-resistance and tumorigenicity of ovarian cancer

TitleLoss of MKP3 is associated with cisplatin-resistance and tumorigenicity of ovarian cancer
Authors
Issue Date2007
PublisherAmerican Association for Cancer Research.
Citation
The 98th Annual Meeting of the American Association for Cancer Research (AACR 2007), Los Angeles, CA., 14-18 April 2007. In Cancer Research, 2007, v. 67 n. 9S, abstract no. 3687 How to Cite?
AbstractThe Ras-Raf-MEK-ERK1/2 (ERK) pathway plays a pivotal role in various cellular responses, including cellular growth, differentiation, survival and motility. Constitutive activation of ERK pathway due to increased exposure to growth factors, overexpression or mutation of receptor tyrosine kinases, Ras and Raf has been linked to many cancers. On the other hand, recent studies have found that the ERK activity is also modulated by a number of negative regulators. In this study, we identified Dual specificity MAPK phophatase 3 (MKP3), one of the negative regulators, was frequently downregulated and correlated with high ERK1/2 activity in human ovarian cancer. Intriguingly, we found that the loss of MKP3 was associated with high intracellular reactive oxygen species (ROS) accumulation such as H2O2. Mild treatment of ovarian cancer cells by hydrogen peroxide H2O2 resulted in MKP3 degradation through proteasome/ubiquitination pathway. Furthermore, enforced expression of MKP3 in MKP3-deficient ovarian cancer cells significantly reduced ERK1/2 activity, sensitized ovarian cancer cells to cisplatin-induced apoptosis, and inhibited cell proliferation and anchorage-independent growth ability in soft agar. These results suggest a molecular mechanism that the accumulation of ROS during ovarian cancer progression may cause the degradation of MKP3, which in turn leads to aberrant ERK1/2 activation and contributes to cisplatin-resistance and tumorigenicity of human ovarian cancer.
Persistent Identifierhttp://hdl.handle.net/10722/95152
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorChan, DWen_HK
dc.contributor.authorLiu, VWSen_HK
dc.contributor.authorFurukawa, Ten_HK
dc.contributor.authorTsao, GSWen_HK
dc.contributor.authorYao, KMen_HK
dc.contributor.authorChan, KKLen_HK
dc.contributor.authorNgan, HYSen_HK
dc.date.accessioned2010-09-25T15:53:16Z-
dc.date.available2010-09-25T15:53:16Z-
dc.date.issued2007en_HK
dc.identifier.citationThe 98th Annual Meeting of the American Association for Cancer Research (AACR 2007), Los Angeles, CA., 14-18 April 2007. In Cancer Research, 2007, v. 67 n. 9S, abstract no. 3687-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/95152-
dc.description.abstractThe Ras-Raf-MEK-ERK1/2 (ERK) pathway plays a pivotal role in various cellular responses, including cellular growth, differentiation, survival and motility. Constitutive activation of ERK pathway due to increased exposure to growth factors, overexpression or mutation of receptor tyrosine kinases, Ras and Raf has been linked to many cancers. On the other hand, recent studies have found that the ERK activity is also modulated by a number of negative regulators. In this study, we identified Dual specificity MAPK phophatase 3 (MKP3), one of the negative regulators, was frequently downregulated and correlated with high ERK1/2 activity in human ovarian cancer. Intriguingly, we found that the loss of MKP3 was associated with high intracellular reactive oxygen species (ROS) accumulation such as H2O2. Mild treatment of ovarian cancer cells by hydrogen peroxide H2O2 resulted in MKP3 degradation through proteasome/ubiquitination pathway. Furthermore, enforced expression of MKP3 in MKP3-deficient ovarian cancer cells significantly reduced ERK1/2 activity, sensitized ovarian cancer cells to cisplatin-induced apoptosis, and inhibited cell proliferation and anchorage-independent growth ability in soft agar. These results suggest a molecular mechanism that the accumulation of ROS during ovarian cancer progression may cause the degradation of MKP3, which in turn leads to aberrant ERK1/2 activation and contributes to cisplatin-resistance and tumorigenicity of human ovarian cancer.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research.-
dc.relation.ispartofCancer Researchen_HK
dc.titleLoss of MKP3 is associated with cisplatin-resistance and tumorigenicity of ovarian canceren_HK
dc.typeConference_Paperen_HK
dc.identifier.emailChan, DW: dwchan@hkucc.hku.hken_HK
dc.identifier.emailLiu, VWS: vwsliu@hkusua.hku.hken_HK
dc.identifier.emailTsao, GSW: gswtsao@hkucc.hku.hken_HK
dc.identifier.emailYao, KM: kmyao@hkusua.hku.hken_HK
dc.identifier.emailChan, KKL: karenchan@pobox.comen_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.authorityChan, DW=rp00543en_HK
dc.identifier.authorityLiu, VWS=rp00341en_HK
dc.identifier.authorityTsao, GSW=rp00399en_HK
dc.identifier.authorityYao, KM=rp00344en_HK
dc.identifier.authorityChan, KKL=rp00499en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.identifier.hkuros130739en_HK

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