title: STMN2 is a novel target of beta-catenin/TCF-mediated transcription in human hepatoma cells.
abstract: The activity of beta-catenin/TCF, the key component of Wnt signaling pathway, is frequently deregulated in human cancers, resulting in the activation of genes whose dysregulation has significant consequences on tumor development. Therefore, identifying the target genes of Wnt signaling is important for understanding beta-catenin-mediated carcinogenesis. Here, we report STMN2, a gene implicated in the regulation of microtubule dynamics, as a novel target of beta-catenin-mediated transcription. STMN2 was up-regulated in hepatoma and cirrhotic liver tissues compared to normal liver and also in cell lines where beta-catenin/TCF is constitutively activated. Transient activation of beta-catenin/TCF either by transfection of a constitutively active form of beta-catenin or by LiCl treatment induced the STMN2 mRNA expression in PLC/PRF/5 cells. Of the four members of STMN gene family, only STMN2 showed a Wnt-dependent expression pattern. Through promoter mapping and chromatin immunoprecipitation assays, we found that STMN2 is a direct target of beta-catenin/TCF-mediated transcription and that the TCF binding site at -1713 of STMN2 promoter is critical for beta-catenin/TCF-dependent expression regulation. siRNA-mediated knock-down of STMN2 expression indicated that STMN2 is required for maintaining the anchorage-independent growth state of beta-catenin/TCF-activated hepatoma cells. Our results suggest that STMN2 might be a novel player of beta-catenin/TCF-mediated carcinogenesis in the liver.
authors.affiliation: Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-600, Republic of Korea.
authors.forename: Heun-Sik
authors.initials: HS
authors.lastname: Lee
authors.forename: Dong Chul
authors.initials: DC
authors.lastname: Lee
authors.forename: Mee-Hee
authors.initials: MH
authors.lastname: Park
authors.forename: Suk-Jin
authors.initials: SJ
authors.lastname: Yang
authors.forename: Jung Ju
authors.initials: JJ
authors.lastname: Lee
authors.forename: Dong Min
authors.initials: DM
authors.lastname: Kim
authors.forename: Yejin
authors.initials: Y
authors.lastname: Jang
authors.forename: Jae-Hyuck
authors.initials: JH
authors.lastname: Lee
authors.forename: Jong Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Kang
authors.forename: Dae Il
authors.initials: DI
authors.lastname: Kim
authors.forename: Kyung Chan
authors.initials: KC
authors.lastname: Park
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Hyang-Sook
authors.initials: HS
authors.lastname: Yoo
authors.forename: Eui-Ju
authors.initials: EJ
authors.lastname: Choi
authors.forename: Young Il
authors.initials: YI
authors.lastname: Yeom
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins; D008870:Microtubules / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D050777:Stathmin; D051822:T Cell Transcription Factor 1 / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; C063314:STMN2 protein, human; D050777:Stathmin; D051822:T Cell Transcription Factor 1; D051176:beta Catenin