Reference - Detail
RRC ID | 41750 |
---|---|
Author | Noda M, Tatsumi Y, Tomizawa M, Takama T, Mitsufuji S, Sugihara H, Kashima K, Hattori T. |
Title | Effects of etodolac, a selective cyclooxygenase-2 inhibitor, on the expression of E-cadherin-catenin complexes in gastrointestinal cell lines. |
Journal | J Gastroenterol |
Abstract |
BACKGROUND:Recent studies have shown that cyclooxygenase-2 (COX-2) inhibitors may participate in the proliferation of cancer cells. Because the cadherin-catenin complex is not only a key component of the adherens junction but also has been suggested to regulate cell proliferation, modulation of these molecules may be a mechanism by which COX-2 activity affects cell proliferation. In this study, we evaluated the effect of a COX-2 inhibitor on the proliferation and expression of E-cadherin-complexes in gastrointestinal cancer cell lines. METHODS:The gastrointestinal cancer cell lines Caco2, HT29, and MKN45 were grown for 24 h in the presence and absence of a selective COX-2 inhibitor, etodolac (10(-5), 10(-4), and 10(-3) M). Cell proliferation was assessed by (3)H-thymidine incorporation, and the expression of E-cadherin and catenins was assessed by Western blotting, Northern blotting, and immunofluorescence. RESULTS:Etodolac induced a significant reduction in cell proliferation in Caco2 and MKN45 cells. E-cadherin expression was upregulated after stimulation with etodolac in Caco2 cells, whereas the expression of alpha-, beta-, gamma- and p120-catenins was not modified. The expression of E-cadherin mRNA was also upregulated in Caco2 cells, and was upregulated also in MKN45 cells, which did not express normal E-cadherin protein by the use of a mouse monoclonal antibody against human E-cadherin, HECD-1 antibody. Immunofluorescence revealed that the increased E-cadherin was localized at the cytoplasmic membrane. CONCLUSIONS:The inhibition of cell growth by etodolac in Caco-2 cells was associated with a dose-dependent upregulation and intense cytoplasmic localization of E-cadherin. No quantitative change in catenin expression was found in this phenomenon. These findings suggest that the COX-2 inhibitor affects the transcription of E-cadherin, or that there may be some homeostatic link between the cell cycle and E-cadherin transcription. |
Volume | 37(11) |
Pages | 896-904 |
Published | 2002-1-1 |
DOI | 10.1007/s005350200151 |
PMID | 12483244 |
MeSH | Animals Caco-2 Cells / drug effects Cadherins / analysis Cadherins / drug effects* Cadherins / genetics Carcinoma / genetics Carcinoma / physiopathology* Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors / pharmacology* Cytoskeletal Proteins / analysis Cytoskeletal Proteins / drug effects* Cytoskeletal Proteins / genetics Desmoplakins Etodolac / pharmacology* Gastrointestinal Neoplasms / genetics Gastrointestinal Neoplasms / physiopathology* Gene Expression / drug effects* Gene Expression / genetics HT29 Cells / drug effects Humans In Vitro Techniques Isoenzymes / antagonists & inhibitors* Isoenzymes / pharmacology* Membrane Proteins Mice Prostaglandin-Endoperoxide Synthases / pharmacology* Trans-Activators / analysis Trans-Activators / drug effects* Trans-Activators / genetics Tumor Cells, Cultured / drug effects* alpha Catenin beta Catenin |
IF | 6.132 |
Times Cited | 35 |
WOS Category | GASTROENTEROLOGY & HEPATOLOGY |
Resource | |
Human and Animal Cells | MKN45(RCB1001) CACO-2(RCB0988) |