Nemo-like kinase induces apoptosis in DLD-1 human colon cancer cells. 2003

Jun Yasuda, and Akira Tsuchiya, and Tesshi Yamada, and Michiie Sakamoto, and Takao Sekiya, and Setsuo Hirohashi
Cancer Transcriptome Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. jyasuda@ncc.go.jp

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.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D003110 Colonic Neoplasms Tumors or cancer of the COLON. Cancer of Colon,Colon Adenocarcinoma,Colon Cancer,Cancer of the Colon,Colon Neoplasms,Colonic Cancer,Neoplasms, Colonic,Adenocarcinoma, Colon,Adenocarcinomas, Colon,Cancer, Colon,Cancer, Colonic,Cancers, Colon,Cancers, Colonic,Colon Adenocarcinomas,Colon Cancers,Colon Neoplasm,Colonic Cancers,Colonic Neoplasm,Neoplasm, Colon,Neoplasm, Colonic,Neoplasms, Colon
D003598 Cytoskeletal Proteins Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. Proteins, Cytoskeletal
D004790 Enzyme Induction An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. Induction, Enzyme
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015534 Trans-Activators Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins. Nuclear Trans-Acting Factor,Trans-Acting Factors,Trans-Acting Factor,Trans-Activator,Transactivator,Transactivators,Factor, Nuclear Trans-Acting,Factor, Trans-Acting,Factors, Trans-Acting,Nuclear Trans Acting Factor,Trans Acting Factor,Trans Acting Factors,Trans Activator,Trans Activators,Trans-Acting Factor, Nuclear
D015870 Gene Expression The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION. Expression, Gene,Expressions, Gene,Gene Expressions
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis

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