Biphasic ER-α36-mediated estrogen signaling regulates growth of gastric cancer cells

To examine the expression patterns of ER-alpha 36 and Cyclin D1 in human gastric cancer tissues and to investigate the effects of ER-alpha 36-mediated estrogen signaling on the growth of gastric cancer cells, 117 samples of formalin-fixed and paraffin-embedded gastric cancer tumor tissues and 40 fresh gastric cancer tumor tissues were analyzed with immunohistochemistry assay and western blot analysis. ER-alpha 36 expression was well correlated with gender (male:female ratio 2.88:1, P=0.01), invasion to serosa (P=0.01) as well as Cyclin D1 expression (P<0.01). The effects of different concentrations of estrogen on the growth of different gastric cancer cells and normal gastric cells as well as gastric cancer SGC7901 cells with different levels of ER-alpha 36 expression were examined. SGC7901 cells with high levels of ER-alpha 36 expression exhibited estrogen hypersensitivity, high growth rate and high levels of Cyclin D1 expression while SGC7901 cells with knocked-down levels of ER-alpha 36 expression were insensitive to estrogen stimulation, grew slowly and expressed less Cyclin D1. Our results indicate that ER-alpha 36 mediates biphasic estrogen signaling in the growth of gastric cancer cells.