Publication: Overexpression of GRP78 and GRP94
is involved in colorectal carcinogenesis
Authors
Takahashi, Hiroyuki ; Wang, Jian-ping ; Zheng, Hua-Chuan ; Masuda, Shinji ; Takano, Yasuo
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Publisher
Editores F. Hernandez y Juan F. Madrid. Murcia, Universidad de Murcia, Departamento de Biologia Celular e Histologia
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Glucose-related proteins (GRPs) are
ubiquitously expressed in the endoplasmic reticulum and
assist in protein folding and assembly, consequently
considered to be molecular chaperones. GRP78 and
GRP94 expression was induced by glucose starvation
and up-regulated in samples taken from several different
malignant tissues. To clarify the roles of both molecules
in tumorigenesis and progression of colorectal
carcinomas, immunohistochemistry (IHC) was performed
on tissue microarrays containing colorectal carcinomas,
adenomas and the non-neoplastic mucosa (NNM) using
antibodies against GRP78 and GRP94. Their expression
was correlated with the clinicopathological parameters
of carcinomas. Both proteins were also studied in
colorectal carcinoma cell lines (DLD-1, HCT-15,
SW480 and WiDr) by IHC and Western blot. There was
a gradually increased GRP78 expression from colorectal
NNMs, carcinomas, to low-grade and high-grade
adenomas (P<0.05), while up-regulated GRP94
expression from NNM, low-grade adenoma, high-grade
adenoma, to carcinoma (P<0.05). The expression was
similar in all the carcinoma cell lines. GRP78 expression
was negatively correlated with lymphatic invasion or
low GRP94 expression of the carcinomas (P<0.05),
while there was no correlation of GRP94 expression
with other parameters of carcinomas (P>0.05).
Multivariate analysis showed that venous invasion,
lymph node metastasis and UICC staging (P<0.05), but
not age, sex, tumor size, differentiation, depth of
invasion, lymphatic invasion, GRP78 and GRP94
expression (P>0.05), were independent prognostic
factors for carcinomas. It is suggested that up-regulated
expression of GRP78 and GRP94 could possibly be
involved in the pathogenesis of colorectal carcinomas.
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