Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China.
Center of Clinical Genetics, Affiliated Bayi Children's Hospital, General Hospital of Beijing Military Command of Chinese PLA, Beijing 100700, China.
Neural Regen Res. 2012 Feb 5;7(4):283-9. doi: 10.3969/j.issn.1673-5374.2012.04.008.
The present study investigated the influence of anti-estrogen treatment (fulvestrant) on pituitary adenoma cell line GH3 biological activity, the estrogen receptor α pathway, the WnT pathway, and mechanisms of decreased Wnt inhibitory factor-1 expression in GH3 cells. Results showed that fulvestrant suppressed GH3 cell proliferation and reduced hormone secretion in a dose-dependent manner. Estrogen receptor α and Wnt4 expression decreased, but Wnt inhibitory factor-1 expression increased in a dose-dependent manner following fulvestrant treatment, and β-catenin expression remained unchanged. Inhibitors of DNA methylation and histone modification upregulated Wnt inhibitory factor-1 expression. Results suggested that fulvestrant suppressed biological activity of GH3 cells via the estrogen receptor α and Wnt pathways. These results suggested that decreased Wnt inhibitory factor-1 expression in GH3 cells played a role in epigenetic mechanisms. Anti-estrogen therapies could provide novel treatments for growth hormone adenomas.
本研究探讨了抗雌激素治疗（氟维司群）对垂体腺瘤细胞系 GH3 生物学活性、雌激素受体 α 通路、WnT 通路以及 GH3 细胞中 Wnt 抑制因子-1 表达降低的机制的影响。结果表明，氟维司群呈剂量依赖性抑制 GH3 细胞增殖并减少激素分泌。雌激素受体 α 和 Wnt4 的表达随氟维司群处理呈剂量依赖性降低，而 Wnt 抑制因子-1 的表达增加，β-连环蛋白的表达保持不变。DNA 甲基化和组蛋白修饰抑制剂上调 Wnt 抑制因子-1 的表达。结果表明，氟维司群通过雌激素受体 α 和 Wnt 通路抑制 GH3 细胞的生物学活性。这些结果表明，GH3 细胞中 Wnt 抑制因子-1 表达的降低在表观遗传机制中发挥作用。抗雌激素治疗可为生长激素腺瘤提供新的治疗方法。
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