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.
Zhao
Dan
D
Department of Gynecology, Peking University People's Hospital, No.11 Nan Da Jie, Xi Zhi Men Beijing 100044, PR China.
Li
Xiao-Ping
XP
Gao
Min
M
Zhao
Chao
C
Wang
Jian-liu
JL
Wei
Li-hui
LH
D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis* / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis* / Q000187:drug effects
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3