Negative regulation of parathyroid hormone-related protein expression by steroid hormones
Negative regulation of parathyroid hormone-related protein expression by steroid hormones
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DOI：
10.1016/j.bbrc.2011.03.037
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发表时间：
2011-04-15
影响因子：
3.1
通讯作者：
Okazaki, Tomoki
中科院分区：
文献类型：
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作者：
Kajitani, Takashi;Tamamori-Adachi, Mimi;Okazaki, Tomoki
甲状旁腺激素相关蛋白（PTHrP）升高与恶性肿瘤体液性高钙血症（HHM）有关，对恶性肿瘤晚期患者的治疗具有重要的临床意义。已知类固醇激素可抑制PTHrP的表达。然而，缺乏将多种类固醇激素与PTHrP表达联系起来的详细研究。在这里，我们研究了四种PTHrP分泌过量的细胞系中PTHrP对类固醇激素的表达。我们的研究证实类固醇激素负性调节PTHrP的表达。同源配体抑制PTHrP的表达需要维生素D受体、雌激素受体a、糖皮质激素受体和孕激素受体。一个明显的例外是雄激素受体，在雄激素处理的细胞中，它对抑制PTHrP表达是必不可少的。我们提出了一个涉及核受体的途径来抑制PTHrP的表达。(C) 2011爱思唯尔公司版权所有。
Elevated parathyroid hormone-related protein (PTHrP) is responsible for humoral hypercalcemia of malignancy (HHM), which is of clinical significance in treatment of terminal patients with malignancies. Steroid hormones were known to cause suppression of PTHrP expression. However, detailed studies linking multiple steroid hormones to PTHrP expression are lacking. Here we studied PTHrP expression in response to steroid hormones in four cell lines with excessive PTHrP production. Our study established that steroid hormones negatively regulate PTHrP expression. Vitamin D receptor, estrogen receptor a, glucocorticoid receptor, and progesterone receptor, were required for repression of PTHrP expression by the cognate ligands. A notable exception was the androgen receptor, which was dispensable for suppression of PTHrP expression in androgen-treated cells. We propose a pathway(s) involving nuclear receptors to suppress PTHrP expression. (C) 2011 Elsevier Inc. All rights reserved.