title: Loss of functional transforming growth factor (TGF)-beta type II receptor results in insensitivity to TGF-beta1-mediated apoptosis and Epstein-Barr virus reactivation.
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.
authors.affiliation: Division of Biosignaling, Department of Biomedical Sciences, School of Life Science, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Fukuda
authors.forename: Hajime
authors.initials: H
authors.lastname: Kurosaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sairenji
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014775:Virus Activation / Q000502:physiology*
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II