Involvement of ER-α36 in the malignant growth of gastric carcinoma cells is associated with GRP94 overexpression

Aims: This study aimed to examine the involvement of glucose-regulated protein 94 (GRP94) in oestrogen receptor-alpha 36 (ER-alpha 36)-mediated oestrogen signalling in gastric cancer development. Methods and results: 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-alpha 36 expression (P < 0.05). Oestrogen treatment up-regulated both GRP94 and ER-alpha 36 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-alpha 36 expression and in xenograft tumours formed by these cells. Forced expression of recombinant ER-alpha 36 in SGC7901 cells, however, up-regulated the levels of GRP94 expression. Conclusions: Glucose-regulated protein 94 is a downstream effector of ER-alpha 36-mediated oestrogen signalling, and may be involved in ER-alpha 36 function during gastric carcinogenesis.