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Yoshiko Kashiwagi, Kuniko Horie, Chikako Kanno, Motoko Inomata, Takashi Imamura, Mitsuyasu Kato, Teiko Yamamoto, Hidetoshi Yamashita; Trichostatin A–Induced TGF-β Type II Receptor Expression in Retinoblastoma Cell Lines. Invest. Ophthalmol. Vis. Sci. 2010;51(2):679-685. doi: 10.1167/iovs.09-4073.
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© ARVO (1962-2015); The Authors (2016-present)
Retinoblastoma, an intraocular malignant tumor of childhood, is caused by a mutation in the retinoblastoma tumor-suppressor gene RB. Retinoblastoma cells are thought to be resistant to transforming growth factor-β (TGF-β) because they do not express the TGF-β type II receptor (TβR-II). In several tumor cell lines, trichostatin A (TSA), a potent inhibitor of histone deacetylase, induces expression of the TβR-II gene. The objective of the present study was to determine the effects of TSA on TβR-II gene expression in retinoblastoma cells.
Four retinoblastoma cell lines were transfected with a TβR-II promoter-luciferase reporter construct and analyzed for the effect of TSA on TβR-II mRNA expression, TβR-II promoter activity, transforming growth factor (TGF)-β–related signal transduction, and cell growth using RT-PCR, Western blot analysis, chromatin immunoprecipitation, luciferase activity assay, and cell viability assays.
TSA treatment induced the expression of TβR-II mRNA, activated the TβR-II promoter, and inhibited cell growth in the examined retinoblastoma cell lines. It did not restore TGF-β–related signaling, however.
These data show that TSA induces the expression of TβR-II mRNA and activates the TβR-II promoter in retinoblastoma cells. However, TSA treatment alone was insufficient to restore TGF-β signaling in these cell lines. The inhibitory effect of TSA on cell growth may be unrelated to its effect on TβR-II expression.
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