title: Overexpression of GRP78 and GRP94 is involved in colorectal carcinogenesis.
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.
authors.affiliation: Department of Pathology, School of Medicine, Kitasato University, Toyama, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Wang
authors.forename: Hua-chuan
authors.initials: HC
authors.lastname: Zheng
authors.forename: Shinji
authors.initials: S
authors.lastname: Masuda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000236:Adenoma / Q000378:metabolism* / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D046888:Tissue Array Analysis; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; C053387:endoplasmin