Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan, China; Jiangda Pathology Institute, Jianghan University, Wuhan, China.
Histopathology. 2013 Sep;63(3):325-33. doi: 10.1111/his.12171. Epub 2013 Jul 8.
This study aimed to examine the involvement of glucose-regulated protein 94 (GRP94) in oestrogen receptor-α36 (ER-α36)-mediated oestrogen signalling in gastric cancer development.
A total of 130 formalin-fixed and paraffin-embedded gastric tumour samples with corresponding normal gastric and tumour-adjacent tissues were used. High levels of GRP94 expression (2+ or 3+) were observed in 109 of 130 gastric carcinomas (83.85%) by immunohistochemistry, and in 13 of 18 tumour specimens (72.22%) with Western blot analysis. GRP94 expression was correlated positively with gender, tumour stage, lymph node metastasis and ER-α36 expression (P < 0.05). Oestrogen treatment up-regulated both GRP94 and ER-α36 expression in gastric cancer SGC7901 cells. In addition, steady state levels of GRP94 protein were decreased in established gastric cancer SGC7901 cells with knocked-down levels of ER-α36 expression and in xenograft tumours formed by these cells. Forced expression of recombinant ER-α36 in SGC7901 cells, however, up-regulated the levels of GRP94 expression.
Glucose-regulated protein 94 is a downstream effector of ER-α36-mediated oestrogen signalling, and may be involved in ER-α36 function during gastric carcinogenesis.
本研究旨在探讨葡萄糖调节蛋白 94（GRP94）在雌激素受体-α36（ER-α36）介导的胃癌发展中雌激素信号转导中的作用。
使用了 130 例福尔马林固定和石蜡包埋的胃癌肿瘤样本，其中包括相应的正常胃组织和肿瘤旁组织。免疫组织化学分析显示，130 例胃癌中有 109 例（83.85%）高表达 GRP94（2+或 3+），Western blot 分析显示 18 例肿瘤标本中有 13 例（72.22%）高表达 GRP94。GRP94 表达与性别、肿瘤分期、淋巴结转移和 ER-α36 表达呈正相关（P<0.05）。雌激素处理可上调胃癌 SGC7901 细胞中 GRP94 和 ER-α36 的表达。此外，在敲低 ER-α36 表达的稳定建立的胃癌 SGC7901 细胞以及由这些细胞形成的异种移植肿瘤中，GRP94 蛋白的稳态水平降低。然而，在 SGC7901 细胞中强制表达重组 ER-α36 可上调 GRP94 的表达。
葡萄糖调节蛋白 94 是 ER-α36 介导的雌激素信号转导的下游效应物，可能参与 ER-α36 在胃癌发生过程中的功能。
