Expression of erythropoietin receptor splice variants in human cancer
Expression of erythropoietin receptor splice variants in human cancer
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DOI：
10.1016/s0006-291x(03)01303-2
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发表时间：
2003-08-08
影响因子：
3.1
通讯作者：
Haroon, ZA
中科院分区：
文献类型：
--
作者：
Arcasoy, MO;Jiang, XH;Haroon, ZA
促红细胞生成素（EPO）通过与其跨膜受体EPOR结合来调节哺乳动物的红细胞生成。最近的研究表明EPOR在人癌细胞中有功能性表达。据报道，重组人EPO刺激乳腺癌和肾癌细胞单层培养物的增殖。此外，在实验动物模型中，给予EPO-EPOR拮抗剂延迟了子宫癌、卵巢癌和乳腺癌细胞的生长。在这项研究中，我们显示EPOR转录和蛋白表达在乳腺癌，结肠癌，肺癌，卵巢癌和前列腺癌细胞。逆转录聚合酶链反应。我们分离并鉴定了癌细胞中表达的EPOR剪接变体的几种新型cDNA。推导的cDNA的氨基酸序列显示剪接变体编码可溶性EPOR或膜结合EPOR肽与胞质内，羧基末端截短。这些发现表明多种EPOR同种型在人癌细胞中的表达，其可调节重组人EPO或EPO-EPOR拮抗剂的细胞效应。(C)2003年爱思唯尔公司All rights reserved.
Erythropoietin (EPO) regulates mammalian erythropoiesis by binding to its transmembrane receptor EPOR. Recent studies demonstrated functional EPOR expression in human cancer cells. Recombinant human EPO was reported to stimulate the proliferation of monolayer cultures of breast and renal carcinoma cells. Furthermore, administration of EPO-EPOR antagonists delayed the growth of uterine, ovarian, and mammary carcinoma cells in experimental animal models. In this study, we show EPOR transcript and protein expression in breast, colon, lung, ovary, and prostate cancer cells. Using reverse transcription-polymerase chain reaction. we isolated and characterized several novel cDNAs for EPOR splice variants expressed in cancer cells. Deduced amino acid sequences of the cDNAs revealed splice variants encoding soluble EPOR or membrane-bound EPOR peptides with intra-cytoplasmic, carboxy-terminal truncations. These findings indicate the expression of multiple EPOR isoforms in human cancer cells that may modulate the cellular effects of recombinant human EPO or EPO-EPOR antagonists. (C) 2003 Elsevier Inc. All rights reserved.