Castelbaum A J, Ying L, Somkuti S G, Sun J, Ilesanmi A O, Lessey B A
Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill 27599, USA.
J Clin Endocrinol Metab. 1997 Jan;82(1):136-42. doi: 10.1210/jcem.82.1.3658.
The pattern of constitutive and cycle-dependent integrins in normal endometrium has recently been established, suggesting a role for cell adhesion molecules in endometrial receptivity and implantation. Currently few, if any, models exist for the study of human endometrial integrins and their role in establishment of the receptive endometrial phenotype. The Ishikawa cell line maintains functional estrogen receptors and progesterone receptors. The progesterone receptors in these cells are inducible by priming with estradiol and down-regulated by treatment with progesterone. In the present study the pattern of integrin expression in this well differentiated endometrial cell line is compared to that in normal endometrial epithelium using immunohistochemistry and flow cytometry and is confirmed by immunoprecipitation, Western immunoblot, and PCR. Like normal endometrial epithelium, Ishikawa cells maintain constitutive expression of alpha 2 beta 1, alpha 3 beta 1, alpha 6 beta 4. PCR demonstrates the expected size fragments of each, although evidence for alternatively spliced forms of the alpha 2-subunit was noted. Progesterone treatment of estradiol-primed cells resulted in increased expression of the alpha 1 beta 1 collagen-laminin receptor and suppression of the alpha v beta 3 vitronectin receptor, two of the cycle-dependent integrins expressed by normal endometrial epithelium. These data support the use of Ishikawa cells as an excellent model to study the regulation endometrial integrins and advance our understanding of hormonally mediated events surrounding implantation.
正常子宫内膜中组成型和周期依赖性整合素的模式最近已被确定,这表明细胞粘附分子在子宫内膜容受性和着床中发挥作用。目前,用于研究人类子宫内膜整合素及其在建立容受性子宫内膜表型中作用的模型很少,即便有也寥寥无几。石川细胞系保留功能性雌激素受体和孕激素受体。这些细胞中的孕激素受体可通过用雌二醇预处理诱导,并通过用孕激素处理而下调。在本研究中,使用免疫组织化学和流式细胞术将这种高度分化的子宫内膜细胞系中的整合素表达模式与正常子宫内膜上皮中的模式进行比较,并通过免疫沉淀、Western免疫印迹和PCR进行确认。与正常子宫内膜上皮一样,石川细胞维持α2β1、α3β1、α6β4的组成型表达。PCR显示了每种整合素预期大小的片段,不过注意到有α2亚基可变剪接形式的证据。用孕激素处理经雌二醇预处理的细胞导致α1β1胶原-层粘连蛋白受体表达增加,而αvβ3玻连蛋白受体表达受到抑制,这是正常子宫内膜上皮表达的两种周期依赖性整合素。这些数据支持将石川细胞用作研究子宫内膜整合素调节的优秀模型,并增进我们对围绕着床的激素介导事件的理解。