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Human Cancer Biology |
Authors' Affiliations: Departments of 1 Molecular and Cellular Oncology and 2 Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas
Requests for reprints: Suresh K. Rayala, Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Box 108, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-745-3559; Fax: 713-794-0209; E-mail: srayala{at}mdanderson.org.
Purpose: This study is intended to investigate the biological role of estrogen receptor (ER) nongenomic signaling in salivary gland adenocarcinoma cells that predominantly express ERß.
Experimental Design: Salivary gland adenocarcinoma cell lines HSG and HSY were used to study the effect of diarylpropionitrile and estrogen on the nongenomic signaling of ERß, cytoskeletal remodeling, and cell motility.
Results: We found that diarylpropionitrile and estrogen triggered rapid activation of the extracellular signal-regulated kinase 1/2 (ERK), Src, and focal adhesion kinase signaling pathways. Estrogen stimulation also induced long cytoplasmic extensions, filopodia formation, and abnormal outgrowths in both HSG and HSY cells. We further observed that ligand-induced migration of these cells was blocked by the pure antiestrogen ICI 182780 and the mitogen-activated protein/ERK kinase inhibitor PD98059, indicating that estrogen-induced cell migration is mediated by the activation of ERß nongenomic signaling.
Conclusion: These results clearly showed that ERß nongenomic signaling is active in salivary gland cells and has a biological role in migration, presumably via the stimulation of ERK1/2. In future, the findings of this study might have clinical importance as several ERß-selective agonists are currently being available, and these could potentially be used for therapeutic targeting of ERß-positive salivary tumors.
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