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

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.

[1]  J. O’Sullivan,et al.  Alterations in the post-translational modification and intracellular trafficking of clusterin in MCF-7 cells during apoptosis , 2003, Cell Death and Differentiation.

[2]  Xiaohang Zhao,et al.  Loss of clusterin both in serum and tissue correlates with the tumorigenesis of esophageal squamous cell carcinoma via proteomics approaches. , 2003, World journal of gastroenterology.

[3]  D. Boothman,et al.  Synthesis and Functional Analyses of Nuclear Clusterin, a Cell Death Protein* , 2003, The Journal of Biological Chemistry.

[4]  I. Trougakos,et al.  Clusterin/apolipoprotein J in human aging and cancer. , 2002, The international journal of biochemistry & cell biology.

[5]  D. Boothman,et al.  Nuclear clusterin/XIP8, an x-ray-induced Ku70-binding protein that signals cell death. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[6]  H. Miyake,et al.  Acquisition of chemoresistant phenotype by overexpression of the antiapoptotic gene testosterone-repressed prostate message-2 in prostate cancer xenograft models. , 2000, Cancer research.

[7]  J. Carver,et al.  Clusterin Has Chaperone-like Activity Similar to That of Small Heat Shock Proteins* , 1999, The Journal of Biological Chemistry.

[8]  L. French,et al.  Clusterin gene expression mediates resistance to apoptotic cell death induced by heat shock and oxidative stress. , 1999, The Journal of investigative dermatology.

[9]  J. Dagorn,et al.  Clusterin overexpression in rat pancreas during the acute phase of pancreatitis and pancreatic development. , 1998, European Journal of Biochemistry.

[10]  Martin R. Schneider,et al.  Estrogenic regulation of clusterin mRNA in normal and malignant endometrial tissue , 1998, International journal of cancer.

[11]  K. Kimura,et al.  Effect of heat shock treatment on the production of variant testosterone‐repressed prostate message‐2 (TRPM‐2) mRNA in culture cells , 1997, Cell biochemistry and function.

[12]  S. North,et al.  Stress-induced transcription of the clusterin/apoJ gene. , 1997, The Biochemical journal.

[13]  George M. Hilliard,et al.  Identification and characterization of glycosylation sites in human serum clusterin , 1997, Protein science : a publication of the Protein Society.

[14]  A. Rademaker,et al.  Intracellular levels of SGP-2 (Clusterin) correlate with tumor grade in prostate cancer. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[15]  M. Griswold,et al.  Expression of clusterin/sulfated glycoprotein-2 under conditions of heat stress in rat Sertoli cells and a mouse Sertoli cell line. , 1997, Journal of andrology.

[16]  P. Howe,et al.  Transforming Growth Factor β (TGFβ)-Induced Nuclear Localization of Apolipoprotein J/Clusterin in Epithelial Cells† , 1996 .

[17]  M. Griswold,et al.  Prevention of cell death induced by tumor necrosis factor alpha in LNCaP cells by overexpression of sulfated glycoprotein-2 (clusterin). , 1995, Cancer research.

[18]  B. Aronow,et al.  Temporally and spatially restricted expression of apolipoprotein J in the developing heart defines discrete stages of valve morphogenesis , 1994, Developmental dynamics : an official publication of the American Association of Anatomists.

[19]  J. Lakins,et al.  Molecular characterization of human TRPM-2/clusterin, a gene associated with sperm maturation, apoptosis and neurodegeneration. , 1994, European journal of biochemistry.

[20]  M. Griswold,et al.  Activity and form of sulfated glycoprotein 2 (clusterin) from cultured Sertoli cells, testis, and epididymis of the rat. , 1994, Biology of reproduction.

[21]  K. Wong,et al.  Induction of gene expression during involution of the lactating mammary gland of the rat. , 1994, Journal of molecular endocrinology.

[22]  P. May.  Sulfated Glycoprotein‐2: An Emerging Molecular Marker for Neurodegeneration , 1993, Annals of the New York Academy of Sciences.

[23]  K. Paizis,et al.  Elevation of human cerebrospinal fluid clusterin concentration is associated with acute neuropathology , 1993, Journal of the Neurological Sciences.

[24]  J. Lakins,et al.  Genomic organization and expression of the rat TRPM-2 (clusterin) gene, a gene implicated in apoptosis. , 1993, The Journal of biological chemistry.

[25]  R. Strange,et al.  Apoptotic cell death and tissue remodelling during mouse mammary gland involution. , 1992, Development.

[26]  K. Grzeschik,et al.  The gene for SP-40,40, human homolog of rat sulfated glycoprotein 2, rat clusterin, and rat testosterone-repressed prostate message 2, maps to chromosome 8. , 1991, Genomics.

[27]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[28]  S. Yeh,et al.  Isolation of Ku70-binding proteins (KUBs). , 1999, Nucleic acids research.

[29]  J. Pedraza-Chaverri,et al.  Induction of clusterin in tubules of nephrotic rats. , 1998, Journal of the American Society of Nephrology : JASN.

[30]  P. Howe,et al.  Transforming growth factor beta (TGF beta)-induced nuclear localization of apolipoprotein J/clusterin in epithelial cells. , 1996, Biochemistry.

[31]  P. Gilna,et al.  Identification of an androgen-repressed mRNA in rat ventral prostate as coding for sulphated glycoprotein 2 by cDNA cloning and sequence analysis. , 1989, The Biochemical journal.