Overexpression of RFT induces G1-S arrest and apoptosis via p53/p21(Waf1) pathway in glioma cell.
The regulator of fibroblast growth factor 2 (FGF-2) transcription (RFT) has been reported to be a transcriptional repressor of FGF-2 and induce glioma cell death by its overexpression. Here we report that RFT regulates cell cycle as well as apoptosis by a novel mechanism. RFT expressed in some glioma cell lines, U138MG and T98G, but neither in U87MG nor U251MG. Overexpressed RFT-induced apoptosis in U87MG and U138MG with functioning-type p53 but neither in U251MG nor T98G with non-functioning-type p53. Administration of FGF-2 failed to prevent RFT-induced apoptosis. Overexpression of RFT caused G1-S arrest and upregulated both the phosphorylation of p53 at Ser-15 and the expression level of p21(Waf1). Furthermore, RNAi knockdown of p53 abolished RFT-induced apoptosis in U87MG. Taken together, our results support that RFT regulates G1-S transition and apoptosis via p53/p21(Waf1) pathway.
Kano
Hideyuki
H
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8315, Japan.
Arakawa
Yoshiki
Y
Takahashi
Jun A
JA
Nozaki
Kazuhiko
K
Kawabata
Yasuhiro
Y
Takatsuka
Kenji
K
Kageyama
Ryoichiro
R
Ueba
Tetsuya
T
Hashimoto
Nobuo
N
D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000502:physiology*; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005455:Fluorescent Antibody Technique; D016193:G1 Phase / Q000502:physiology*; D005910:Glioma / Q000473:pathology*; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D016196:S Phase / Q000502:physiology*; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017931:DNA Primers; D004268:DNA-Binding Proteins; C066141:MBD1 protein, human; D012097:Repressor Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53