Tumor necrosis factor-related apoptosis-inducing ligand induces apoptotic cell death through c-Jun NH2-terminal kinase activation in squamous cell carcinoma cells. 2009

Takenori Noutomi, and Mizue Itoh, and Hiroko Toyota, and Eiko Takada, and Junichiro Mizuguchi
Department of Immunology and Intractable Immune System Disease Research Center, Tokyo Medical University, Tokyo 160-8402, Japan.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in MIT6 cells derived from primary oral squamous cell carcinoma (OSCC), whereas it does not induce apoptosis in MIL6 cells derived from metastases. The present studies were performed to examine whether activation of c-Jun NH2-terminal kinase (JNK) is implicated in the differential sensitivity to TRAIL-induced apoptosis. The TRAIL-induced JNK activation in MIT6 cells was stronger than in MIL6 cells, as assessed by Western blotting using antibodies specific for phospho-JNK. To evaluate the role of JNK1 in TRAIL-induced cell death, one clone expressing the dominant-negative form of JNK1 (dnJNK1) was established. The dnJNK1-expressing cells and MIL6 cells expressed TRAIL protein at levels similar to or even greater than MIT6 cells did. When cell death was assessed by annexin V staining and mitochondrial membrane potential, kinetic studies demonstrated that the dnJNK1-expressing cells were substantially more resistant to 100 ng/ml TRAIL, comparable to MIL6 cells, at 36 and 48 h after stimulation. Collectively, the primary OSCC cell line, MIT6, is sensitive to TRAIL but its metastatic line MIL6 is resistant to TRAIL exposure. Thus, the underlying molecular mechanism of TRAIL-induced cell death involves JNK activation. These results suggest that the acquisition of TRAIL resistance provides some metastatic capacity to primary tumors.

UI MeSH Term Description Entries
D009062 Mouth Neoplasms Tumors or cancer of the MOUTH. Cancer of Mouth,Mouth Cancer,Oral Cancer,Oral Neoplasms,Cancer of the Mouth,Neoplasms, Mouth,Neoplasms, Oral,Cancer, Mouth,Cancer, Oral,Cancers, Mouth,Cancers, Oral,Mouth Cancers,Mouth Neoplasm,Neoplasm, Mouth,Neoplasm, Oral,Oral Cancers,Oral Neoplasm
D002294 Carcinoma, Squamous Cell A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed) Carcinoma, Epidermoid,Carcinoma, Planocellular,Carcinoma, Squamous,Squamous Cell Carcinoma,Carcinomas, Epidermoid,Carcinomas, Planocellular,Carcinomas, Squamous,Carcinomas, Squamous Cell,Epidermoid Carcinoma,Epidermoid Carcinomas,Planocellular Carcinoma,Planocellular Carcinomas,Squamous Carcinoma,Squamous Carcinomas,Squamous Cell Carcinomas
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D005434 Flow Cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D005799 Genes, Dominant Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state. Conditions, Dominant Genetic,Dominant Genetic Conditions,Genetic Conditions, Dominant,Condition, Dominant Genetic,Dominant Gene,Dominant Genes,Dominant Genetic Condition,Gene, Dominant,Genetic Condition, Dominant
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
D015153 Blotting, Western Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes. Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings
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
D048031 JNK Mitogen-Activated Protein Kinases A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION. jun N-Terminal Kinase,c-jun Amino-Terminal Kinase,c-jun N-Terminal Kinase,jun-NH2-Terminal Kinase,jun-NH2-Terminal Kinases,Amino-Terminal Kinase, c-jun,JNK Mitogen Activated Protein Kinases,Kinase, jun N-Terminal,N-Terminal Kinase, c-jun,N-Terminal Kinase, jun,c jun Amino Terminal Kinase,c jun N Terminal Kinase,jun N Terminal Kinase,jun NH2 Terminal Kinase,jun NH2 Terminal Kinases

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