Autocrine erythropoietin signaling inhibits hypoxia-induced apoptosis in human breast carcinoma cells
Autocrine erythropoietin signaling inhibits hypoxia-induced apoptosis in human breast carcinoma cells
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DOI：
10.1016/j.canlet.2004.04.027
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发表时间：
2004-10-28
期刊：
影响因子：
9.7
通讯作者：
Koch, CJ
中科院分区：
文献类型：
--
作者：
Acs, G;Chen, M;Koch, CJ
灌注紊乱和由此产生的缺氧是赋予肿瘤异质性的重要特征，这可能导致复发。缺氧的肿瘤细胞与对辐射和细胞毒性药物的抵抗力有关。缺氧还可能通过促进某些细胞的凋亡和扩大凋亡潜力降低的变异体来充当肿瘤的选择压力，从而在更具侵袭性的表型的发展中发挥作用。缺氧诱导的促红细胞生成素（Epo）控制红细胞生成，并在保护神经元免受缺氧损伤方面发挥作用。我们最近证明了人类乳腺癌和宫颈癌中缺氧刺激的 Epo 和 Epo 受体 (EpoR) 的表达，表明自分泌 Epo 信号在癌症缺氧适应中的作用。在当前的研究中，我们提供的证据表明，中等水平缺氧诱导的自分泌 Epo 信号增强可抑制缺氧诱导的细胞凋亡并促进 MCF-7 人乳腺癌细胞的存活。 Epo 的抗凋亡作用与 bcl-2 和 bCI-X-L 的上调相关，表明其机制与造血细胞中描述的机制类似。由此导致的缺氧肿瘤细胞的凋亡潜力降低可能导致乳腺癌的侵袭性和治疗耐药性增加。 (C) 2004 Elsevier Ireland Ltd. 保留所有权利。
Disordered perfusion and the resulting hypoxia are important features conferring tumor heterogeneity, which may contribute to relapse. Hypoxic tumor cells have been associated with resistance both to radiation and to cytotoxic drugs. Hypoxia may also serve as a selection pressure in tumors by promoting apoptosis of some cells and expanding variants with decreased apoptotic potential, and thus play a role in the development of a more aggressive phenotype. Erythropoietin (Epo), induced by hypoxia, controls erythropoiesis and plays a role in protection of neurons from hypoxic damage. We have recently demonstrated hypoxia-stimulated expression of Epo and Epo receptor (EpoR) in human breast and cervix cancers, suggesting a role for autocrine Epo signaling in the hypoxic adaptations of carcinomas. In the current study we provide evidence that increased autocrine Epo signaling induced by moderate levels of hypoxia inhibits hypoxia-induced apoptosis and promotes survival in MCF-7 human breast cancer cells. The anti-apoptotic effect of Epo correlates with upregulation of bcl-2 and bCI-X-L, suggesting a mechanism similar to those described in hematopoictic cells. The resulting decreased apoptotic potential of hypoxic tumor cells may contribute to increased aggressiveness and therapy resistance of breast cancers. (C) 2004 Elsevier Ireland Ltd. All rights reserved.