Molecular and Cellular Gynecological Endocrinology Laboratory, Department of Reproductive Medicine and Child Development, University of Pisa, Pisa, Italy.
Fertil Steril. 2011 Feb;95(2):722-6. doi: 10.1016/j.fertnstert.2010.08.039. Epub 2010 Sep 25.
To explore the effects of 17β-estradiol (E(2)) on cytoskeletal remodeling and motility of endometrial stromal cells (ESC) and Ishikawa cells and to characterize the role of focal adhesion kinase (FAK) in these processes.
In vitro study of cytoskeletal remodeling and cellular morphology and motility in ESC or Ishikawa cells.
University research center.
PATIENT(S): Endometrial samples obtained from women requiring endometrial biopsies.
INTERVENTION(S): Treatments with E(2) and multiple inhibitors of signaling pathways.
MAIN OUTCOME MEASURE(S): Activation of FAK, actin remodeling, membrane morphology, cell motility, and invasion.
RESULT(S): Estrogen induces a rapid and concentration-related FAK phosphorylation in ESC and Ishikawa cells. In this time frame, FAK localizes to the plasma membrane at sites of focal adhesion complexes formation, as shown by immunofluorescence. Phosphorylation of FAK in the presence of estrogen depends on the recruitment of both estrogen receptor α and estrogen receptor β and of a rapid G protein-dependent signaling to c-Src and phosphatidylinositol 3-OH kinase. Activation of FAK in ESC and Ishikawa cells is required for estrogen-induced horizontal migration and invasion of three-dimensional matrices of endometrial cells.
CONCLUSION(S): Estrogen enhances cytoskeletal and membrane remodeling in ESC and Ishikawa cells by controlling FAK, thus resulting in enhanced cell motility and invasion. These findings may have clinical relevance for the development of new therapeutic strategies for the prevention or control of endometrial diseases.
探讨 17β-雌二醇（E2）对子宫内膜基质细胞（ESC）和 Ishikawa 细胞细胞骨架重塑和运动的影响，并探讨局灶黏附激酶（FAK）在这些过程中的作用。
体外研究 ESC 或 Ishikawa 细胞中细胞骨架重塑和细胞形态及运动的变化。
大学研究中心。
需要子宫内膜活检的女性的子宫内膜样本。
用 E2 和多种信号通路抑制剂进行处理。
FAK 的激活、肌动蛋白重塑、膜形态、细胞运动和侵袭。
雌激素诱导 ESC 和 Ishikawa 细胞中快速且呈浓度依赖性的 FAK 磷酸化。在此时间范围内，免疫荧光显示 FAK 定位于形成黏附斑复合物的质膜部位。雌激素存在时 FAK 的磷酸化依赖于雌激素受体 α 和雌激素受体 β 的募集以及快速的 G 蛋白依赖性信号转导至 c-Src 和磷脂酰肌醇 3-OH 激酶。ESC 和 Ishikawa 细胞中 FAK 的激活是雌激素诱导的水平迁移和子宫内膜细胞三维基质侵袭所必需的。
雌激素通过控制 FAK 增强 ESC 和 Ishikawa 细胞的细胞骨架和膜重塑，从而增强细胞运动和侵袭。这些发现可能对预防或控制子宫内膜疾病的新治疗策略的发展具有临床意义。
