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Invest Ophthalmol Vis Sci. 2010 Feb;51(2):679-85. doi: 10.1167/iovs.09-4073. Epub 2009 Sep 8.

Trichostatin A-induced TGF-beta type II receptor expression in retinoblastoma cell lines.

Author information

1
Department of Ocular Cellular Engineering, Yamagata University Faculty of Medicine, Yamagata City, Yamagata, Japan. kasiwagi@med.id.yamagata-u.ac.jp

Abstract

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 (TbetaR-II). In several tumor cell lines, trichostatin A (TSA), a potent inhibitor of histone deacetylase, induces expression of the TbetaR-II gene. The objective of the present study was to determine the effects of TSA on TbetaR-II gene expression in retinoblastoma cells.

METHODS:

Four retinoblastoma cell lines were transfected with a TbetaR-II promoter-luciferase reporter construct and analyzed for the effect of TSA on TbetaR-II mRNA expression, TbetaR-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 TbetaR-II mRNA, activated the TbetaR-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 TbetaR-II mRNA and activates the TbetaR-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 TbetaR-II expression.

PMID:
19737884
DOI:
10.1167/iovs.09-4073
[Indexed for MEDLINE]

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