Trichostatin A-Induced TGF-β Type II Receptor Expression in Retinoblastoma Cell Lines

PURPOSE. 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-beta (TGF-beta) because they do not express the TGF-beta type II receptor (T beta R-II). In several tumor cell lines, trichostatin A (TSA), a potent inhibitor of histone deacetylase, induces expression of the T beta R-II gene. The objective of the present study was to determine the effects of TSA on T beta R-II gene expression in retinoblastoma cells. METHODS. Four retinoblastoma cell lines were transfected with a T beta R-II promoter-luciferase reporter construct and analyzed for the effect of TSA on T beta R-II mRNA expression, T beta R-II promoter activity, transforming growth factor (TGF)-beta-related signal transduction, and cell growth using RT-PCR, Western blot analysis, chromatin immunoprecipitation, luciferase activity assay, and cell viability assays. RESULTS. TSA treatment induced the expression of T beta R-II mRNA, activated the T beta R-II promoter, and inhibited cell growth in the examined retinoblastoma cell lines. It did not restore TGF-beta-related signaling, however. CONCLUSIONS. These data show that TSA induces the expression of T beta R-II mRNA and activates the T beta R-II promoter in retinoblastoma cells. However, TSA treatment alone was insufficient to restore TGF-beta signaling in these cell lines. The inhibitory effect of TSA on cell growth may be unrelated to its effect on T beta R-II expression. (Invest Ophthalmol Vis Sci. 2010; 51: 679-685) DOI: 10.1167/iovs.09-4073