GRP78 positively regulates estrogen-stimulated cell growth mediated by ER-alpha 36 in gastric cancer cells

摘要

Estrogen receptor (ER)-alpha 36, a novel isoform of ER, primarily mediates non-classical estrogen signaling. It has been reported that ER-alpha 36-mediated growth stimulating signals are involved in the malignancy of gastric tumor cells. However, the mechanism underlying the regulation of ER-alpha 36 function in development of gastric cancer remains to be elucidated. The present study investigated the role of 78 kDa glucose-regulated protein (GRP78) in the regulation of ER-alpha 36 expression and signaling during the growth of gastric tumor cells. It was demonstrated that GRP78 expression was detectable in gastric cancer tumor tissues, and was positively-correlated with tumor stage, lymphatic metastasis and ER-alpha 36 expression (P<0.05). An increased growth rate, and increased expression of ER-alpha 36 and the cell cycle regulator cyclin D1 was detected in cells with GRP78 overexpression (SGC-High78 cells). SGC-High78 cells are more sensitive to estrogen compared with SGC-Control cells. Therefore, the results of the present study demonstrated that GRP78 positively regulated ER-alpha 36 expression and signaling with cell growth in gastric cancer, which is involved in gastric carcinogenesis.