Stromal cell-derived factor 1α 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-la (SDF-1 alpha) 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 lshikawa 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-1 alpha, MAPK-specific inhibitor PD98059 or PI3K-specific inhibitor LY294002. Results. Low concentrations of SDF-1 alpha (<= 50 ng/ml) significantly promoted proliferation of Ishikawa cells but not of HEC-1A, while high concentrations of SDF-1 alpha (> 50 ng/ml) induced proliferation in both cell lines. ERK1/2 was significantly activated for more than 2 It by SDF-1 alpha at 20 ng/ml in HEC-1A cells, but not in Ishikawa cells. In contrast, Akt was significantly activated for over 2 It in Ishikawa cells but remained unchanged in HEC-1A cells. High concentrations of SDF-1 alpha activated Akt and ERK 1/2 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-1 alpha 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. (c) 2006 Elsevier Inc. All rights reserved.