RASSF1A and the Taxol Response in Ovarian Cancer

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RASSF1A and the Taxol Response in Ovarian Cancer

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Title: RASSF1A and the Taxol Response in Ovarian Cancer
Author: Kassler, Susannah; Donninger, Howard; Clark, Geoffrey J.; Birrer, Michael James

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Citation: Kassler, Susannah, Howard Donninger, Michael J. Birrer, and Geoffrey J. Clark. 2012. RASSF1A and the taxol response in ovarian cancer. Molecular Biology International 2012:263267.
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Abstract: The RASSF1A tumor suppressor gene is frequently inactivated by promoter methylation in human tumors. The RASSF1A protein forms an endogenous complex with tubulin and promotes the stabilization of microtubules. Loss of RASSF1A expression sensitizes cells to microtubule destabilizing stimuli. We have observed a strong correlation between the loss of RASSF1A expression and the development of Taxol resistance in primary ovarian cancer samples. Thus, we sought to determine if RASSF1A levels could dictate the response to Taxol and whether an epigenetic therapy approach might be able to reverse the Taxol resistant phenotype of RASSF1A negative ovarian tumor cells. We found that knocking down RASSF1A expression in an ovarian cancer cell line inhibited Taxol-mediated apoptosis and promoted cell survival during Taxol treatment. Moreover, using a combination of small molecule inhibitors of DNA Methyl Transferase enzymes, we were able restore RASSF1A expression and Taxol sensitivity. This identifies a role for RASSF1A in modulating the tumor response to Taxol and provides proof of principal for the use of epigenetic therapy to overcome Taxol resistance.
Published Version: doi:10.1155/2012/263267
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3324163/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10347178
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