Upregulated claudin-1 expression confers resistance to cell death of nasopharyngeal carcinoma cells

Int J Cancer. 2010 Mar 15;126(6):1353-66. doi: 10.1002/ijc.24857.

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

  • Antimetabolites, Antineoplastic / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Blotting, Western
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Claudin-1
  • Culture Media, Serum-Free / pharmacology
  • Drug Resistance, Neoplasm / genetics
  • Fluorouracil / pharmacology
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Microscopy, Confocal
  • NF-kappa B / metabolism
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Up-Regulation

Substances

  • Antimetabolites, Antineoplastic
  • CLDN1 protein, human
  • Cadherins
  • Claudin-1
  • Culture Media, Serum-Free
  • Membrane Proteins
  • NF-kappa B
  • Green Fluorescent Proteins
  • Proto-Oncogene Proteins c-akt
  • Fluorouracil