title: β-catenin/Tcf-4 complex transcriptionally regulates AKT1 in glioma.
abstract: Increasing evidence suggests that interplays between Wnt/β-catenin and PI3K/AKT signaling cascades are involved in tumor development and progression. However, the exact mechanism in glioma is not well known. Using aspirin, we found that the expression levels of AKT1 in glioma cells significantly correlated with the transcriptional activity of β-catenin. Similar observations were made when we subjected glioma cells to treatment with Tcf4 siRNA. Moreover, both aspirin and Tcf4 siRNA can suppress the proliferation and induce apoptosis of glioma. In addition, our analysis of the gene promoter of AKT1 revealed multiple putative Tcf-4 binding sites. In support of the concept that β-catenin/Tcf-4 is a transcriptional regulator for AKT1, results from our chromatin immunoprecipitation studies and luciferase assay showed that β-catenin/Tcf-4 binds to the potential binding sites in the gene promoter of AKT1. Furthermore, using immunohistochemistry, we found that Tcf-4 protein expression increased significantly in high-grade glioma in comparison to low-grade glioma and correlated with AKT1 expression. In conclusion, our results support the concept that β-catenin/Tcf-4 directly regulates AKT1 in glioma, and these two proteins may cooperate with each other in exerting their oncogenic effects in glioma.
authors: Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, PR China.
authors: Lingchao
authors: L
authors: Chen
authors: Kai
authors: K
authors: Huang
authors: Lei
authors: L
authors: Han
authors: Zhendong
authors: Z
authors: Shi
authors: Kailiang
authors: K
authors: Zhang
authors: Peiyu
authors: P
authors: Pu
authors: Chuanlu
authors: C
authors: Jiang
authors: Chunsheng
authors: C
authors: Kang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C495270:CTNNB1 protein, human; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051176:beta Catenin; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D001241:Aspirin