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


CONCLUSIONS
The N-terminal deletion of clusterin may be essential for its alterations of biogenesis in ESCC.
He
Hong-Zhi
HZ
National Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Song
Zhen-Mei
ZM
Wang
Kun
K
Teng
Liang-Hong
LH
Liu
Fang
F
Mao
You-Sheng
YS
Lu
Ning
N
Zhang
Shang-Zhong
SZ
Wu
Min
M
Zhao
Xiao-Hang
XH
D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D051152:Clusterin; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*
C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones