Arcasoy Murat O, Jiang Xiaohong, Haroon Zishan A
Department of Medicine, Division of Hematology-Medical Oncology, Duke University School of Medicine, DUMC Box 3912, Durham, NC 27710, USA.
Biochem Biophys Res Commun. 2003 Aug 8;307(4):999-1007. doi: 10.1016/s0006-291x(03)01303-2.
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.
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。最近的研究表明人癌细胞中存在功能性EPOR表达。据报道，重组人促红细胞生成素能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拮抗剂可延缓子宫、卵巢和乳腺癌细胞的生长。在本研究中，我们展示了乳腺癌、结肠癌、肺癌、卵巢癌和前列腺癌细胞中EPOR转录本和蛋白的表达。利用逆转录-聚合酶链反应，我们分离并鉴定了几种在癌细胞中表达的新型EPOR剪接变体的cDNA。这些cDNA推导的氨基酸序列显示，剪接变体编码具有胞质内、羧基末端截短的可溶性EPOR或膜结合EPOR肽。这些发现表明人癌细胞中存在多种EPOR异构体，它们可能调节重组人促红细胞生成素或EPO-EPOR拮抗剂的细胞效应。
