Department of Pathology, School of Medicine, Kitasato University, Toyama, Japan.
Histol Histopathol. 2011 Jun;26(6):663-71. doi: 10.14670/HH-26.663.
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.
葡萄糖相关蛋白（GRPs）广泛表达于内质网，协助蛋白质折叠和组装，因此被认为是分子伴侣。葡萄糖饥饿可诱导 GRP78 和 GRP94 的表达，且在来自多种恶性组织样本中上调。为了阐明这两种分子在结直肠癌发生和进展中的作用，使用针对 GRP78 和 GRP94 的抗体，对包含结直肠癌、腺瘤和非肿瘤性黏膜（NNM）的组织微阵列进行免疫组织化学（IHC）。将其表达与癌的临床病理参数相关联。还通过 IHC 和 Western blot 在结直肠癌细胞系（DLD-1、HCT-15、SW480 和 WiDr）中研究了这两种蛋白。GRP78 表达从结直肠 NNM、癌到低级别和高级别腺瘤逐渐增加（P<0.05），而 GRP94 表达从 NNM、低级别腺瘤、高级别腺瘤到癌上调（P<0.05）。在所有癌细胞系中表达相似。GRP78 表达与淋巴浸润或癌中低 GRP94 表达呈负相关（P<0.05），而 GRP94 表达与癌的其他参数无相关性（P>0.05）。多变量分析显示静脉侵犯、淋巴结转移和 UICC 分期（P<0.05），但不是年龄、性别、肿瘤大小、分化、浸润深度、淋巴浸润、GRP78 和 GRP94 表达（P>0.05），是癌的独立预后因素。提示 GRP78 和 GRP94 的上调表达可能参与了结直肠癌的发病机制。
