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Loss of functional transforming growth factor (TGF)-beta type II receptor results in insensitivity to TGF-beta1-mediated apoptosis and Epstein-Barr virus reactivation.

Research paper by Makoto M Fukuda, Hajime H Kurosaki, Takeshi T Sairenji

Indexed on: 26 Sep '06Published on: 26 Sep '06Published in: Journal of Medical Virology



Abstract

Transforming growth factor (TGF)-beta1 induces not only cell growth inhibition or apoptosis but also Epstein-Barr virus (EBV) reactivation in some Burkitt's lymphoma (BL) cell lines. The purpose of this study was to define the role of TGF-beta signaling molecules in response to TGF-beta1-mediated cell growth inhibition, apoptosis, and EBV reactivation in BL cell lines. First, we confirmed the effect of TGF-beta1 on the cell growth and EBV reactivation in six BL cell lines. TGF-beta1 induced cell growth inhibition and EBV reactivation in these cell lines but did not in Akata cells. To elucidate the mechanism of TGF-beta1 unresponsiveness in Akata cells, we studied the expression of TGF-beta receptors and the intracellular signaling molecules Smads. All cell lines expressed TGF-beta type I receptor, Smad2, Smad3, and Smad4. TGF-beta type II receptor (R-II) was expressed in all cell lines except Akata cells. Introduction of the TGF-beta R-II into Akata cells results in sensitivity to TGF-beta1-mediated growth inhibition, apoptosis, and EBV reactivation. In addition, to test a possibility to the transcriptional repression of the TGF-beta R-II gene in Akata cells, the effect of histone deacetylation (HDAC) inhibitor, trichostatin A (TSA) was examined. The expression of TGF-beta R-II in Akata cells was induced by TSA treatment. These results suggest that the lack of functional TGF-beta R-II impedes the progression of signals through TGF-beta1 and becomes a determinant of unresponsiveness to TGF-beta1-mediated growth inhibition and EBV reactivation.