title: ER-α36-mediated gastric cancer cell proliferation via the c-Src pathway.
abstract: Previously, a novel variant of estrogen receptor (ER)-α, ER-α36, was identified and cloned and reported to mainly mediate non-genomic estrogen signaling. More recently, we identified that ER-α36 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-α36 in SGC7901 gastric cancer cells. SGC7901 cells were subjected to the siRNA-mediated knockdown of ER-α36 (PLKO.1-PURO-SP6-ER-α36-L) or transfected with an ER-α36 upregulated expression plasmid (PLJM1-ER-α36-H) and treated with 17β-estradiol (E2β) and PP2, a c-Src protein inhibitor. The expression of ER-α36 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-α36, was shown to enhance gastric cancer cell proliferation through activation of the membrane-initiated c-Src signaling pathways, indicating that ER-α36 is important for the regulation of proliferation in gastric cancer. In addition, ER-α36 was shown to directly interact with c-Src by immunoprecipitation. The results of the present study indicate that the use of ER-α36 may be a targeted therapeutic approach in gastric cancer.
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medical Science of Wuhan University, P.R. China.
authors.forename: Xuming
authors.initials: X
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Deng
authors.forename: Feng
authors.initials: F
authors.lastname: Zou
authors.forename: Zhenqi
authors.initials: Z
authors.lastname: Fu
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhaoyi
authors.initials: Z
authors.lastname: Wang
authors.forename: Lijiang
authors.initials: L
authors.lastname: Liu
keywords: ER-α36; c-src; cyclin D1; gastric cancer; proliferation