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Proapoptotic ability of oncogenic H-Ras to facilitate apoptosis induced by histone deacetylase inhibitors in human cancer cells
Molecular Cancer Therapeutics (2007)
  • SHAMBHUNATH CHOUDHARY, University of Tennessee - Knoxville
  • Hwa-Chain Robert Wang, University of Tennessee - Knoxville
Abstract

More than 35% of human urinary bladder cancers involve oncogenic H-Ras activation. In addition to tumorigenic ability, oncogenic H-Ras possesses a novel proapoptotic ability to facilitate the induction of apoptosis by histone deacetylase inhibitors (HDACI). HDACIs are a new class of anticancer agents and are highly cytotoxic to transformed cells. To understand the connection between the selectivity of HDACIs on transformed cells and the proapoptotic ability of oncogenic H-Ras to facilitate HDACI-induced apoptosis, we introduced oncogenic H-Ras into urinary bladder J82 cancer cells to mimic an acquisition of the H-ras gene activation in tumor development. Expression of oncogenic H-Ras promoted J82 cells to acquire tumorigenic ability. Meanwhile, oncogenic H-Ras increased susceptibility of J82 cells to HDACIs, including FR901228 and trichostatin A, for inducing apoptosis. The caspase pathways, the B-Raf and extracellular signal-regulated kinase pathway, p21Cip1 and p27Kip1, and core histone contents are regulated differently by FR901228 in oncogenic H-Ras–expressed J82 cells than their counterparts in parental J82 cells, contributing to the increased susceptibility to the induction of selective apoptosis. Our results lead us to a suggestion that HDACIs activate the proapoptotic ability of oncogenic H-Ras, indicating a potential therapeutic value of this new class of anticancer agents in the control of human urinary bladder cancer that has progressed to acquire oncogenic H-Ras

Keywords
  • proapoptotic Ras,
  • histone deacetylase inhibitor,
  • signaling pathway,
  • therapeutic target urinary,
  • bladder cancer
Publication Date
2007
Citation Information
SHAMBHUNATH CHOUDHARY and Hwa-Chain Robert Wang. "Proapoptotic ability of oncogenic H-Ras to facilitate apoptosis induced by histone deacetylase inhibitors in human cancer cells" Molecular Cancer Therapeutics Vol. 6 Iss. 3 (2007)
Available at: http://works.bepress.com/shambhunath_choudhary/7/