Involvement of the Akt signaling pathway in ER-α36/GRP94-mediated signaling in gastric cancer.

ABSTRACT

Glucose-regulated protein 94 (GRP94) has been implicated in the promotion of tumor proliferation and metastasis. Previous studies have found that GRP94 is involved in the malignant growth of gastric carcinoma cells through estrogen receptor-α36 (ER-α36)-mediated estrogen signaling, but the underlying mechanism remains unclear. In the present study, we examined the expression levels of GRP94 and ER-α36 in tumor specimens from gastric cancer patients by immunohistochemistry, and found that both GRP94 and ER-α36 were highly expressed in the cytoplasms of gastric carcinoma cells. Furthermore, treatment with 17ß-estradiol at a concentration of 10-12 M for 24 h increased the expression levels of GRP94 and ER-α36, and the phosphorylation levels of Akt at the Ser473 site (Ser473-Akt). In established SGC7901 gastric cancer cells with knockdown of ER-α36 expression, the levels of GRP94 and Ser473-Akt expression were significantly reduced. Thus, the Akt signaling pathway is a potentially important signaling pathway in ER-α36-GRP94-mediated gastric carcinogenesis.