RRC ID 43954
著者 Nagao H, Setoguchi T, Kitamoto S, Ishidou Y, Nagano S, Yokouchi M, Abematsu M, Kawabata N, Maeda S, Yonezawa S, Komiya S.
タイトル RBPJ is a novel target for rhabdomyosarcoma therapy.
ジャーナル PLoS One
Abstract The Notch pathway regulates a broad spectrum of cell fate decisions and differentiation processes during fetal and postnatal development. In addition, the Notch pathway plays an important role in controlling tumorigenesis. However, the role of RBPJ, a transcription factor in the Notch pathway, in the development of tumors is largely unknown. In this study, we focused on the role of RBPJ in the pathogenesis of rhabdomyosarcoma (RMS). Our data showed that Notch pathway genes were upregulated and activated in human RMS cell lines and patient samples. Inhibition of the Notch pathway by a γ-secretase inhibitor (GSI) decreased the in vitro proliferation of RMS cells. Knockdown of RBPJ expression by RNAi inhibited the anchorage-independent growth of RMS cells and the growth of xenografts in vivo. Additionally, overexpression of RBPJ promoted the anchorage-independent growth of RMS cells. Further, we revealed that RBPJ regulated the cell cycle in RMS xenograft tumors and decreased proliferation. Our findings suggest that RBPJ regulates the RMS growth, and that the inhibition of RBPJ may be an effective therapeutic approach for patients with RMS.
巻・号 7(7)
ページ e39268
公開日 2012-1-1
DOI 10.1371/journal.pone.0039268
PII PONE-D-12-06292
PMID 22792167
PMC PMC3392254
MeSH Animals Carbamates / pharmacology Cell Line, Tumor Cell Proliferation Dibenzazepines / pharmacology Dipeptides / pharmacology Gene Expression Regulation, Neoplastic / drug effects Gene Knockdown Techniques Humans Immunoglobulin J Recombination Signal Sequence-Binding Protein / genetics* Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism Mice Mice, Nude RNA Interference Receptors, Notch / metabolism Rhabdomyosarcoma / genetics* Rhabdomyosarcoma / pathology Rhabdomyosarcoma / therapy Signal Transduction / drug effects Tumor Burden / genetics Xenograft Model Antitumor Assays
IF 2.74
引用数 12
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 RMS-YM(RCB1695)