Evidence that corticotropin-releasing hormone inhibits cell growth of human breast cancer cells via the activation of CRH-R1 receptor subtype
Evidence that corticotropin-releasing hormone inhibits cell growth of human breast cancer cells via the activation of CRH-R1 receptor subtype
复制标题
DOI：
10.1016/j.mce.2006.10.006
复制
发表时间：
2007-01-29
影响因子：
4.1
通讯作者：
Navarra, Pierluigi
中科院分区：
文献类型：
--
作者：
Graziani, Grazia;Tentori, Lucio;Navarra, Pierluigi
先前已表明，促肾上腺皮质激素释放激素（CRH）对雌激素依赖性肿瘤细胞系，即人子宫内膜腺癌石川（IK）细胞发挥抗增殖活性。在这里，我们研究了 CRH 对另一种雌激素依赖性肿瘤细胞系——人乳腺癌 MCF7 细胞的影响。在此范例中，在孵育 48 和 72 It 后，以 100 nM 固定浓度给予 CRH 显着抑制 100 nM 雌二醇 (E2) 诱导的细胞生长。该作用与细胞凋亡的诱导无关。非选择性 CRH 受体拮抗剂 astressin 以及 CRH-R1 选择性受体拮抗剂 antalarmin 以浓度依赖性方式抵消 CRH 对细胞增殖的抑制。在基础条件下对 MCF7 进行的 RNase 保护测定表明，这些细胞以组成型方式表达 CRH-R1 受体亚型。我们还研究了 CRH 作用于乳腺癌细胞的假定来源；我们发现MCF7细胞在基础条件下表达CRH mRNA并分泌大量免疫反应性CRH，这导致推测乳腺癌细胞中存在由CRH操纵的旁分泌-自分泌抑制机制。 (c) 2006 Elsevier Ireland Ltd. 保留所有权利。
It has been previously shown that corticotropin-releasing hormone (CRH) exerts antiproliferative activity on an estrogen-dependent tumor cell line, i.e. human endometrial adenocarcinoma Ishikawa (IK) cells. Here we have investigated the effects of CRH on another estrogen-dependent tumor cell line, human breast cancer MCF7 cells. In this paradigm, CRH given at a fixed concentration of 100 nM significantly inhibited cell growth induced by 100 nM estradiol (E2) after 48 and 72 It of incubation. This effect was not associated with the induction of apoptosis. CRH inhibition of cell proliferation was counteracted in a concentration-dependent manner by the non-selective CRH receptor antagonist, astressin, as well as by a CRH-R1 selective receptor antagonist, antalarmin. RNase protection assays carried out on MCF7 under basal conditions showed that these cells express in a constitutive manner the CRH-R1 receptor subtype. We have also investigated the putative source of CRH acting on breast cancer cells; we found that MCF7 cells express CRH mRNA under basal conditions and secrete sizable amounts of immunoreactive CRH, which leads to postulate the existence of paracrine-autocrine inhibitory mechanism operated by CRH in breast cancer cells. (c) 2006 Elsevier Ireland Ltd. All rights reserved.