ERK/CANP rapid signaling mediates 17β-estradiol-induced proliferation of human breast cancer cell line MCF-7 cells

International Journal of Clinical and Experimental Medicine

Huan Li¹  Yan-Gang Huang¹  Shi-Jie Bi¹  Guo-Sheng Wang¹  Jin-Long Zhao¹ 

关键词: Breast cancer cell;    estradiol;    cell proliferation;    extracellular signal-regulated kinase;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Objective: 17β-estradiol (E2) exerts its functions through both genomic and non-genomic signaling pathways. Because E2 is important in breast cancer development, we investigated whether its actions in promoting breast cancer cell proliferation occur through the non-genomic signaling pathway via extracellular signal-regulated kinase 1/2 (ERK1/2)/calcium-activated neutral protease (CANP). Methods: MCF-7 breast cancer cells were treated with ERKl/2 inhibitor (PD98059) or CANP inhibitor (calpeptin) before exposure to 1×10^-8 M E2. MTT colorimetry and flow cytometry were used to analyze effects on cell proliferation and cell cycle progression, respectively. Expression of phosphorylated-ERK (p-ERK), total ERK, and Capn4 proteins were assessed by Western blotting. Results: Cell proliferation increased in cells treated with E2 for 24 h (P<0.05), and the proportion of cells in G₀/G₁ was decreased, accompanied by accelerated G₁/S. Calpeptin pre-treatment significantly inhibited the E₂-induced proliferation of MCF-7 cells (P<0.05), while also ameliorating the effects of E2 on cell cycle progression. Further, expression of p-ERK was rapidly up-regulated (after 10 min) by E2 (P<0.05), an effect that persisted 16 h after E2 exposure but which was significantly inhibited by PD98059 (P<0.05). Conclusions: Finally, expression of Capn4 protein was rapidly up-regulated in E2-exposed cells (P<0.05), but this change was significantly inhibited by PD98059 or calpeptin (P<0.05) pre-treatment. Thus, the rapid, non-genomic ERK/CANP signaling pathway mediates E₂-induced proliferation of human breast cancer cells.

【 授权许可】

Unknown