title: Nemo-like kinase induces apoptosis in DLD-1 human colon cancer cells.
abstract: Deregulation of Wnt/beta-catenin signaling is thought to play a critical role in human carcinogenesis. Nemo-like kinase (NLK) is an evolutionarily conserved serine/threonine kinase that suppresses beta-catenin/T-cell factor (TCF) complex transcriptional activity through phosphorylation of TCF. Since NLK may be a tumor suppressor as a negative regulator of Wnt/beta-catenin pathway, we established tetracycline-inducible NLK and its kinase-negative mutant expression in DLD-1 human colon cancer cells to analyze the effect of NLK on cell growth and viability. The induction of wild-type NLK in DLD-1 cells caused suppression of cell growth whereas the kinase-negative mutant did not. Flow cytometry indicated that NLK expression increased the number of apoptotic cells but did not induce obvious cell cycle arrest. Apoptosis induction by wild-type NLK was confirmed using TUNEL assays. Our results suggest that overexpression of NLK may have targets other than TCF for induction of apoptosis in human colon carcinoma cells.
authors.affiliation: Cancer Transcriptome Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. jyasuda@ncc.go.jp
authors.forename: Jun
authors.initials: J
authors.lastname: Yasuda
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuchiya
authors.forename: Tesshi
authors.initials: T
authors.lastname: Yamada
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Takao
authors.initials: T
authors.lastname: Sekiya
authors.forename: Setsuo
authors.initials: S
authors.lastname: Hirohashi
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000502:physiology; D004790:Enzyme Induction; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D017346:Protein Serine-Threonine Kinases; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology; D014407:Tumor Cells, Cultured; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015534:Trans-Activators; D051176:beta Catenin; C470551:NLK protein, human; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases