Stromal Cell-derived Factor 1alpha Stimulates Human Endometrial Carcinoma Cell Growth Through the Activation of Both Extracellular Signal-regulated Kinase 1/2 and Akt

Objective: The aim of study was to investigate the proliferative effects of stromal cell-derived factor-1alpha (SDF-1alpha) on endometrial carcinomas cell lines with different estrogen receptors (ER) and PTEN protein profiles.

Methods: MTT assays was used to detect the proliferation of HEC-1A and Ishikawa cells, and Western blotted analysis was used to detect activation of Akt and ERK1/2 in both cell lines after exposure to various concentrations of SDF-1alpha, MAPK-specific inhibitor PD98059 or PI3K-specific inhibitor LY294002.

Results: Low concentrations of SDF-1alpha (<or=50 ng/ml) significantly promoted proliferation of Ishikawa cells but not of HEC-1A, while high concentrations of SDF-1alpha (>50 ng/ml) induced proliferation in both cell lines. ERK1/2 was significantly activated for more than 2 h by SDF-1alpha at 20 ng/ml in HEC-1A cells, but not in Ishikawa cells. In contrast, Akt was significantly activated for over 2 h in Ishikawa cells but remained unchanged in HEC-1A cells. High concentrations of SDF-1alpha activated Akt and ERK1/2 pathways in both cell lines in a dose-dependent manner, which was primarily inhibited by LY294002 for pAkt and by PD98059 for pERK 1/2.

Conclusions: SDF-1alpha could stimulate the cell proliferation of endometrial carcinoma with different expression status of ER and PTEN in vitro, likely through the activation of both Akt and ERK1/2 signaling pathways.