【摘 要】
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Purpose: Endometrial stromal sarcoma (ESS) is a rare gynecological malignancy with an unclear molecular pathogenesis and thus few therapeutic options.Histone deacetylase (HDAC) 2 expression was shown
【机 构】
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Medical University of Graz Austria
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Purpose: Endometrial stromal sarcoma (ESS) is a rare gynecological malignancy with an unclear molecular pathogenesis and thus few therapeutic options.Histone deacetylase (HDAC) 2 expression was shown to be upregulated in human ESS specimens.The HDAC inhibitor SAHA reduced in vitro growth of the ESS cell line ESS-1 through the inhibition ofmTOR signaling.The PI3K/Akt/mTOR signaling, central to translational regulation, growth and survival of cancer cells is an important target in cancer therapy.This study aimed at investigating (1) if HDAC and the PI3K/Akt/mTOR signaling are involved in ESS pathogenesis and (2) how altered HDAC levels regulate PI3K/Akt/mTOR signaling and its downstream translation regulators in ESS.Methods: The expression levels of HDAC 1 and 2 in ESS were examined on a tissue microarray.The mRNA and protein levels of HDAC 1 and 2 were determined by Q-PCR and Western blotting in ESS cell lines (ESS-1 and MESSA) and the appropriate control endometrial stromal cell line HESC.The role of HDAC in regulating the PI3K signaling was checked in cells treated with SAHA.Results:1.HDAC 1 and 2 are overexpressed in ESS tissues, compared to normal endometrium.2.Higher levels of HDAC1 and 2, increased cell growth, upregulatedAkt and mTOR activation were detected in ESS cellscompared to HESCcell lines.3.SAHA inhibited cell growth of three cell lines.Conclusions: HDACs and the PI3K signaling are involved in ESS pathogenesis.Despite of different drug sensitivity and response rates among all cell lines, SAHA reduced cell growth via the PI3K/Alt/mTOR signaling and its downstream effectors 4EBP1 and p70S6K, indicating an integration of HDACs with the PI3K signaling and translation regulation.
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