To determine whether estrogen receptor-α36 (ER-α36) -mediated rapid estrogen signaling is associated with 78 kDa glucose-regulated protein (GRP78) expression in gastric cancer, 86 samples of gastric tumor tissue with corresponding normal and tumor-adjacent tissues were used to examine expression patterns of GRP78 and ER-α36. Immunohistochemistry demonstrated that 55/86 (63.95%) patients with gastric carcinoma, and western blot analysis revealed that GRP78 was upregulated in 15/20 (75%) of tumor specimens. GRP78 expression was positively associated with ER-α36 expression, the male sex and lymph node metastasis (P<0.05). Estrogen treatment increased GRP78 and ER-α36 expression, as well as GSK-3β phosphorylation in established gastric cancer SGC-7901 cells. The steady-state level of GRP78 protein expression and the level of phosphorylated GSK-3β at Ser9 were decreased in SGC-7901 cells with ER-α36 knockdown. Forced expression of ER-α36 in SGC-7901 cells, however, led to an increase in GRP78 expression and GSK-3β phosphorylation. It may therefore be concluded that ER-α36-mediated rapid estrogen signaling positively regulates GRP78 expression, presumably via the GSK-3β pathway, which may be associated with gastric carcinogenesis.
Keywords: 78 kDa glucose-regulated protein; estrogen receptor-α36; estrogen signaling; gastric cancer; glycogen synthasekinase-3β.