Gamma-secretase complexes regulate the responses of human pancreatic ductal adenocarcinoma cells to taxanes. 2010

Takehiko Tasaka, and Takashi Akiyoshi, and Koji Yamaguchi, and Masao Tanaka, and Hideya Onishi, and Mitsuo Katano
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

OBJECTIVE It was previously reported that γ-secretase inhibitors (GSIs) enhance taxane-induced mitotic arrest and apoptosis in colon cancer cells. To enable the development of taxane-based chemotherapy for pancreatic ductal adenocarcinoma (PDAC), this study investigated the molecular mechanisms by which γ-secretase (GS) complexes regulate taxane sensitivity. METHODS The effect of GS complexes on taxane-induced apoptosis in PDAC cells was evaluated by a cell cycle analysis. GS complexes were examined with small interference RNAs targeted to GS complex-related genes. RESULTS GSIs and silencing of presenilin 1 (PS1) did not affect cell proliferation but resulted in enhanced taxane-induced G(2)/M accumulation and apoptosis. Silencing of the Notch gene did not induce these effects. However, PS2-specific silencing suppressed proliferation and taxane-induced apoptosis. CONCLUSIONS Data from this study indicate that GS complexes regulate the response of PDAC to taxanes through GS-dependent and GS-independent mechanisms.

UI MeSH Term Description Entries
D010190 Pancreatic Neoplasms Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA). Cancer of Pancreas,Pancreatic Cancer,Cancer of the Pancreas,Neoplasms, Pancreatic,Pancreas Cancer,Pancreas Neoplasms,Pancreatic Acinar Carcinoma,Pancreatic Carcinoma,Acinar Carcinoma, Pancreatic,Acinar Carcinomas, Pancreatic,Cancer, Pancreas,Cancer, Pancreatic,Cancers, Pancreas,Cancers, Pancreatic,Carcinoma, Pancreatic,Carcinoma, Pancreatic Acinar,Carcinomas, Pancreatic,Carcinomas, Pancreatic Acinar,Neoplasm, Pancreas,Neoplasm, Pancreatic,Neoplasms, Pancreas,Pancreas Cancers,Pancreas Neoplasm,Pancreatic Acinar Carcinomas,Pancreatic Cancers,Pancreatic Carcinomas,Pancreatic Neoplasm
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D004151 Dipeptides Peptides composed of two amino acid units. Dipeptide
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
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
D043823 Taxoids A group of diterpenoid CYCLODECANES named for the taxanes that were discovered in the TAXUS tree. The action on MICROTUBULES has made some of them useful as ANTINEOPLASTIC AGENTS. Taxanes,Taxoid
D051880 Receptors, Notch A family of conserved cell surface receptors that contain EPIDERMAL GROWTH FACTOR repeats in their extracellular domain and ANKYRIN REPEATS in their cytoplasmic domains. The cytoplasmic domains are released upon ligand binding and translocate to the CELL NUCLEUS, where they act as transcription factors. Notch Protein,Notch Receptor,Notch Receptors,Notch Proteins,Protein, Notch,Receptor, Notch

Related Publications

Takehiko Tasaka, and Takashi Akiyoshi, and Koji Yamaguchi, and Masao Tanaka, and Hideya Onishi, and Mitsuo Katano
March 2012, The Journal of experimental medicine,
Takehiko Tasaka, and Takashi Akiyoshi, and Koji Yamaguchi, and Masao Tanaka, and Hideya Onishi, and Mitsuo Katano
September 2023, Cancer research communications,
Takehiko Tasaka, and Takashi Akiyoshi, and Koji Yamaguchi, and Masao Tanaka, and Hideya Onishi, and Mitsuo Katano
January 2016, Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.],
Takehiko Tasaka, and Takashi Akiyoshi, and Koji Yamaguchi, and Masao Tanaka, and Hideya Onishi, and Mitsuo Katano
May 2009, Gastroenterology,
Takehiko Tasaka, and Takashi Akiyoshi, and Koji Yamaguchi, and Masao Tanaka, and Hideya Onishi, and Mitsuo Katano
June 2022, Matrix biology : journal of the International Society for Matrix Biology,
Takehiko Tasaka, and Takashi Akiyoshi, and Koji Yamaguchi, and Masao Tanaka, and Hideya Onishi, and Mitsuo Katano
July 2023, Nature communications,
Takehiko Tasaka, and Takashi Akiyoshi, and Koji Yamaguchi, and Masao Tanaka, and Hideya Onishi, and Mitsuo Katano
April 2019, Cancer research,
Takehiko Tasaka, and Takashi Akiyoshi, and Koji Yamaguchi, and Masao Tanaka, and Hideya Onishi, and Mitsuo Katano
January 1999, Diabetes,
Takehiko Tasaka, and Takashi Akiyoshi, and Koji Yamaguchi, and Masao Tanaka, and Hideya Onishi, and Mitsuo Katano
December 2020, Journal of cancer research and clinical oncology,
Takehiko Tasaka, and Takashi Akiyoshi, and Koji Yamaguchi, and Masao Tanaka, and Hideya Onishi, and Mitsuo Katano
January 2012, Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.],
Copied contents to your clipboard!