Lorincz M A, Holt J A, Greene G L
J Clin Endocrinol Metab. 1985 Sep;61(3):412-7. doi: 10.1210/jcem-61-3-412.
Based on previous studies of the properties of moxestrol, we hypothesized that a radiohalogenated analog of moxestrol, [125I]11 beta-methoxy-17 alpha-iodovinyl-estradiol [( 125I] MIVE2), should bind to the estrogen receptor (ER) in some ovarian adenocarcinomas (OVCA), thereby offering the potential for imaging and/or treatment of these cancers. We used monoclonal antibodies (H222, H226, and D547) against human breast cancer ER to identify the [125I]MIVE2-binding moiety in OVCA cytosols that is found on high salt sucrose gradients. After gel electrophoresis and western blotting, exposure of OVCA extracts to the ER antibodies, followed by exposure to goat antirat serum and then rat peroxidase antiperoxidase, demonstrated a moiety in OVCA that migrated indistinguishably from the ER in MCF-7 human breast cancer cells and from that in specimens of breast cancer tissue. Because few studies have demonstrated efficacy of hormone management for OVCA, we also wanted to learn whether ER exists in multiple forms in OVCA, in view of the possibility that some forms may be inactive in regulating growth-dependent cell functions while retaining estrogen-binding capacity. By incubating the monoclonal antibodies H222, H226, and D547, each of which recognizes a different region on the ER protein, with OVCA cytosol fractions, we demonstrated that ER in OVCA can exist in multiple forms, some of which fail to express an H226-recognized site and some of which fail to express a D547-recognized site. This observation indicates that a relationship may exist between the presence or absence of certain forms of ER in ovarian epithelial cancer and a patient's response to hormone therapy.
基于先前对莫昔司醇性质的研究，我们推测莫昔司醇的放射性卤代类似物[125I]11β-甲氧基-17α-碘乙烯基雌二醇([125I]MIVE2)，应该能与某些卵巢腺癌(OVCA)中的雌激素受体(ER)结合，从而为这些癌症的成像和/或治疗提供可能性。我们使用针对人乳腺癌ER的单克隆抗体(H222、H226和D547)来鉴定在高盐蔗糖梯度上发现的OVCA胞质溶胶中[125I]MIVE2结合部分。经过凝胶电泳和蛋白质印迹分析，将OVCA提取物先与ER抗体接触，再与山羊抗大鼠血清接触，然后与大鼠过氧化物酶抗过氧化物酶接触，结果显示OVCA中有一个部分，其迁移情况与MCF-7人乳腺癌细胞中的ER以及乳腺癌组织标本中的ER无法区分。由于很少有研究证明激素管理对OVCA有效，鉴于某些形式的ER在调节生长依赖性细胞功能方面可能无活性但仍保留雌激素结合能力，我们还想了解OVCA中ER是否以多种形式存在。通过将单克隆抗体H222、H226和D547(每种抗体识别ER蛋白上的不同区域)与OVCA胞质溶胶组分一起孵育，我们证明OVCA中的ER可以以多种形式存在，其中一些不表达H226识别的位点，一些不表达D547识别的位点。这一观察结果表明，卵巢上皮癌中某些形式的ER的存在与否与患者对激素治疗的反应之间可能存在关联。
