科研之友
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摘要
Previously, a novel variant of estrogen receptor (ER)-alpha, ER-alpha 36, was identified and cloned and reported to mainly mediate non-genomic estrogen signaling. More recently, we identified that ER-alpha 36 is important for the invasion and lymph node metastasis of human gastric cancer. In the present study, the c-Src signaling pathway was demonstrated to be involved in the non-genomic estrogen signaling mediated by ER-alpha 36 in SGC7901 gastric cancer cells. SGC7901 cells were subjected to the siRNA-mediated knockdown of ER-alpha 36 (PLKO.1-PURO-SP6-ER-alpha 36-L) or transfected with an ER-alpha 36 upregulated expression plasmid (PLJM1-ER-alpha 36-H) and treated with 17 beta-estradiol (E2 beta) and PP2, a c-Src protein inhibitor. The expression of ER-alpha 36 and c-src/p-c-Src and cyclin D1 was examined by western blot analysis, and tumor cell growth was analyzed by cell proliferation and nude mouse xenograft assays. The ER variant, ER-alpha 36, was shown to enhance gastric cancer cell proliferation through activation of the membrane-initiated c-Src signaling pathways, indicating that ER-alpha 36 is important for the regulation of proliferation in gastric cancer. In addition, ER-alpha 36 was shown to directly interact with c-Src by immunoprecipitation. The results of the present study indicate that the use of ER-alpha 36 may be a targeted therapeutic approach in gastric cancer.
