Hata H, Hata K, Hamano M, Shimoda T, Kuramoto H
Department of Obstetrics and Gynecology, Kitasato University School of Medicine, Sagamihara, Japan.
Hum Cell. 1989 Sep;2(3):265-71.
The responsiveness and action mechanisms of steroid hormones and epidermal growth factor on human endometrial carcinoma cells are analyzed by using in vitro culture system. 1) The Ishikawa cells, derived from a well differentiated endometrial adenocarcinoma and possess ER and PR, are shown to respond to estrogens by increasing a variety of parameters, viz cell proliferation, PR levels, ALP and DNA polymerase activities. 2) ER and PR of those cells are localized in the nuclei by immunocytochemical staining using the monoclonal antibodies against to ER and PR, confirming the correctness of Gorski and Greene's one step theory involving the action mechanisms of steroid hormones. 3) Progestins reduced the ER level and stimulate E2DH activities and glycogen content, which are completely abolished by anti-progestin (RU486), suggesting that PR of those cells should be functional. 4) These responses to steroid hormones of Ishikawa cells are synergistically enhanced or appeared earlier by addition of EGF. 5) The main metabolite of E2 incubated with Ishikawa cells is E2-3-sulfate instead of E1, indicate that the higher estrogenic status may be persisted in endometrial cancer tissues.
利用体外培养系统分析了甾体激素和表皮生长因子对人子宫内膜癌细胞的反应性及作用机制。1)源自高分化子宫内膜腺癌且具有雌激素受体(ER)和孕激素受体(PR)的 Ishikawa 细胞,通过增加多种参数,即细胞增殖、PR 水平、碱性磷酸酶(ALP)和 DNA 聚合酶活性,显示出对雌激素有反应。2)使用抗 ER 和 PR 的单克隆抗体通过免疫细胞化学染色将这些细胞的 ER 和 PR 定位在细胞核中,证实了 Gorski 和 Greene 关于甾体激素作用机制的一步理论的正确性。3)孕激素降低 ER 水平并刺激 E2DH 活性和糖原含量,而抗孕激素(RU486)可完全消除这些作用,表明这些细胞的 PR 应具有功能。4)通过添加表皮生长因子(EGF),Ishikawa 细胞对甾体激素的这些反应协同增强或出现得更早。5)与 Ishikawa 细胞一起孵育的雌二醇(E2)的主要代谢产物是 E2 - 3 - 硫酸盐而非雌酮(E1),表明子宫内膜癌组织中可能持续存在较高的雌激素状态。