Abstract
Accumulating evidence reveals that aberrant expression of claudins manifests in various tumors; however, their biological functions are poorly understood. Here, we report on the elevated expression of claudin-1 in nasopharyngeal carcinoma (NPC) cell lines under serum deprivation or fluorouracil (5-FU) treatment. Interestingly, an increase in expression of claudin-1 considerably reduced apoptosis rather than enhancing cell proliferation. However, claudin-1 expression and activity were unaffected by external stimuli or Akt and NF-kappaB activation. Notably, predominant cytoplasmic and nuclear localization of claudin-1 in NPC cells reflected the aforementioned feature. On the other hand, loss of epithelial morphology and E-cadherin expression was associated with serum withdrawal in NPC cells. Interestingly, restoration of E-cadherin inhibited the protein elevation and antiapoptotic activity of claudin-1. In conclusion, our data demonstrate the regulation and novel biological function of claudin-1 and indicate the important role of claudin-1 in NPC tumorigenesis.
MeSH terms
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Antimetabolites, Antineoplastic / pharmacology
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Apoptosis / drug effects
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Apoptosis / genetics*
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Blotting, Western
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Cadherins / genetics
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Cadherins / metabolism
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Cell Line
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Claudin-1
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Culture Media, Serum-Free / pharmacology
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Drug Resistance, Neoplasm / genetics
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Fluorouracil / pharmacology
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Gene Expression Profiling*
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Gene Expression Regulation, Neoplastic*
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Humans
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism
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Microscopy, Confocal
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NF-kappa B / metabolism
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Nasopharyngeal Neoplasms / genetics
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Nasopharyngeal Neoplasms / metabolism
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Nasopharyngeal Neoplasms / pathology
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Oligonucleotide Array Sequence Analysis
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Proto-Oncogene Proteins c-akt / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / drug effects
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Up-Regulation
Substances
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Antimetabolites, Antineoplastic
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CLDN1 protein, human
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Cadherins
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Claudin-1
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Culture Media, Serum-Free
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Membrane Proteins
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NF-kappa B
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Green Fluorescent Proteins
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Proto-Oncogene Proteins c-akt
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Fluorouracil