Ohshiro Kazufumi, Rayala Suresh K, Williams Michelle D, Kumar Rakesh, El-Naggar Adel K
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):5994-9. doi: 10.1158/1078-0432.CCR-06-1251.
This study is intended to investigate the biological role of estrogen receptor (ER) nongenomic signaling in salivary gland adenocarcinoma cells that predominantly express ERbeta.
Salivary gland adenocarcinoma cell lines HSG and HSY were used to study the effect of diarylpropionitrile and estrogen on the nongenomic signaling of ERbeta, cytoskeletal remodeling, and cell motility.
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 ERbeta nongenomic signaling.
These results clearly showed that ERbeta 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 ERbeta-selective agonists are currently being available, and these could potentially be used for therapeutic targeting of ERbeta-positive salivary tumors.
本研究旨在探讨雌激素受体（ER）非基因组信号在主要表达ERβ的涎腺腺癌细胞中的生物学作用。
使用涎腺腺癌细胞系HSG和HSY来研究二芳基丙腈和雌激素对ERβ非基因组信号、细胞骨架重塑及细胞运动性的影响。
我们发现二芳基丙腈和雌激素可快速激活细胞外信号调节激酶1/2（ERK）、Src和粘着斑激酶信号通路。雌激素刺激还诱导HSG和HSY细胞出现长的细胞质延伸、丝状伪足形成及异常生长。我们进一步观察到，这些细胞的配体诱导迁移被纯抗雌激素ICI 182780和丝裂原活化蛋白/ERK激酶抑制剂PD98059阻断，表明雌激素诱导的细胞迁移是由ERβ非基因组信号的激活介导的。
这些结果清楚地表明，ERβ非基因组信号在涎腺细胞中具有活性，并且在迁移中具有生物学作用，推测是通过刺激ERK1/2实现的。未来，本研究的发现可能具有临床重要性，因为目前有几种ERβ选择性激动剂，这些可能潜在地用于ERβ阳性涎腺肿瘤的治疗靶向。
