Rapid signaling pathway of ERK/ CANP partially mediates 17β-estradiol-induced proliferation in human breast cancer cell line MCF-7
10.3781/j.issn.1000-7431.2011.02.007
- Author:
Yang CAO
1
Author Information
1. Department of Physiology
- Publication Type:Journal Article
- Keywords:
Breast neoplasms;
Calpain;
Cell proliferation;
Estradiol;
Extracellular signal-regulated kinase;
In vitro
- From:
Tumor
2011;31(2):126-130
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate a possible role of extracellular signal-regulated kinase (ERK) 1/2/ calcium-activated neutral protease (CANP) signaling pathway in 17β-estradiol (E2)-induced proliferation of human breast cancer cell line MCF-7. Methods: MCF-7 cells were pretreated with ERK1/2 inhibitor PD98059 or CANP inhibitor calpeptin, and then treated with 1×10-8 mol/L E2. MTT assay was employed to determine the effect on cell proliferation. Cell cycle distribution was detected by flow cytometry (FCM). The expression levels of phosphorylated-ERK (p-ERK), total ERK and CANP small subunit Capn4 proteins were examined by Western blotting. Results: The proliferation rate was increased in MCF-7 cells treated with 1×10-8 mol/L E2 for 24 h (P<0.01). The number of cells in G0/ G1 phase was decreased, and the accelerated G1/S transition was observed. Calpeptin could significantly inhibited E2-induced proliferation of MCF-7 cells (P<0.01). The number of cells in G0/G1 phase was increased, and the delayed G1/S transition was observed. The expression of p-ERK was rapidly up-regulated (during 10 minutes) induced by E2 (P<0.01), and this effect persisted for at least 16 h; but there was no obvious change in the expression of total ERK. E2-induced ERK phosphorylation in MCF-7 cells was significantly inhibited by PD98059 (P<0.01). The expression of Capn4 protein was rapidly up-regulated in E2-induced MCF-7 cells ( P<0.01) while significantly inhibited by PD98059 or calpeptin (P<0.01) in MCF-7 cells. Conclusion: The rapid signaling pathway of ERK/ CANP is involved in E2-induced proliferation of human breast cancer cells.
