Alterations in expression, proteolysis and intracellular localizations of clusterin in esophageal squamous cell carcinoma

World J Gastroenterol. 2004 May 15;10(10):1387-91. doi: 10.3748/wjg.v10.i10.1387.

Abstract

Aim: To investigate biogenesis and intracellular localizations of clusterin to elucidate the potential molecular mechanisms implicated in tumorigenesis of esophageal mucosa.

Methods: Semi-quantitative RT-PCR for multi-region alteration analysis, Western blot for different transcriptional forms and immunohistochemical staining for intracellular localizations of clusterin were carried out in both tissues and cell lines of ESCC.

Results: The N-terminal deletions of the clusterin gene and the appearance of a 50-53 ku nuclear clusterin, an uncleaved, nonglycosylated, and disulfide-linked isoform, were the major alterations in cancer cells of esophagus. Naturally the 40 ku clusterin was located in the connective tissue of the lamina propria of epithelial mucosa and right under the basal membrane of epithelia, but it was disappeared in stromal mucosa of esophagus and the pre-matured clusterin was found positive in cancerous epithelia.

Conclusion: The N-terminal deletion of clusterin may be essential for its alterations of biogenesis in ESCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Clusterin
  • Down-Regulation
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Esophagus / anatomy & histology
  • Esophagus / metabolism
  • Esophagus / pathology
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*

Substances

  • CLU protein, human
  • Clusterin
  • Glycoproteins
  • Molecular Chaperones