Class II histone deacetylases play pivotal roles in heat shock protein 90-mediated proteasomal degradation of vascular endothelial growth factor receptors
Section snippets
Materials and methods
Reagents. Antibody to HDAC6 (H-300) was obtained from Santa Cruz Biotechnology, Inc (Santa Cruz, CA, USA). Antibody to HDAC10 was purchased from Biovision Research Products (Mountain View, CA, USA). 17-AAG, an Hsp90 inhibitor, and antibodies to Hsp90 (SPA-830) and Hsp70/Hsc70 (SPA-820) were purchased from Stressgen (Victoria, British Columbia, Canada). Proteasomal inhibitors (MG132, Lactacystin), were obtained from Sigma (St. Louis, MO, USA). SAHA and LAQ824 were provided by In2Gen Co. (Seoul,
HDIs induced the depletion of VEGFR proteins in cancer cells
In order to assess the effects of HDI treatment on the expression of the VEGFR family, we initially examined the levels of VEGFR family protein (VEGFR-1, VEGFR-2, and VEGFR-3) expression in human lung cancer cells (HCT116) and human gastric cancer cells (SNU-620) following treatment with hydroxamate-based HDI, including SAHA and LAQ824. Interestingly, among these 3 proteins, VEGFR-1 and VEGFR-2 were determined to have been downregulated after SAHA treatment in a time-dependent manner in both
Acknowledgments
This study was supported in part by grants from Seoul National University Hospital (Grant #: 03-2006-012-0) and by the BK21 Project for Medicine, Dentistry, and pharmacy. We thank the members of Dr. Bang’s laboratory for helpful discussion.
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