Erythropoietin gene expression in renal carcinoma is considerably more frequent than paraneoplastic polycythemia
Erythropoietin gene expression in renal carcinoma is considerably more frequent than paraneoplastic polycythemia
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DOI：
10.1002/ijc.22961
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发表时间：
2007-12-01
影响因子：
6.4
通讯作者：
Eckardt, Kai-Uwe
中科院分区：
文献类型：
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作者：
Wiesener, Michael S.;Muenchenhagen, Philine;Eckardt, Kai-Uwe
促红细胞生成素 (EPO) 信号传导越来越被认为是肿瘤生物学中的相关机制，可能导致增殖、血管生成和治疗耐药性增强。癌性 EPO 过量产生引起的副肿瘤性红细胞增多症很少见，但最常见于肾细胞癌 (RCC) 患者。大多数透明细胞肾细胞癌表现出调节 EPO 的转录因子（缺氧诱导因子 (HIF)）的强烈激活。因此，目前还不清楚为什么只有一小部分患者会出现红细胞增多症。我们研究了 70 个 RCC 的 EPO 基因和 HIF α 亚型表达。 34% 的 RCC 在 RNase 保护测定中显示 EPO mRNA 表达，这几乎完全是透明细胞类型。只有我的患者出现红细胞增多症。原位杂交显示EPO在肿瘤细胞中表达。 EPO mRNA 的表达始终与 HIF 的激活相关，这可能涉及 HIF-1 α 和/或 HIF-2 α。因此，肾细胞癌中 EPO 基因表达的频率远高于红细胞增多症的患病率。此外，HIF 的激活似乎是 RCC 中 EPO 基因表达所必需的，但显然不是唯一的决定因素。除了报道的 EPO 受体在肿瘤组织中的表达之外，EPO 在 RCC 中广泛表达的发现支持了最近的观点，即该系统参与肿瘤细胞的旁分泌或自分泌作用。 (C) 2007 Wiley-Liss, Inc.
Signalling by erythropoietin (EPO) is increasingly recognised as a relevant mechanism in tumour biology, potentially leading to enhanced proliferation, angiogenesis and therapy resistance. Paraneoplastic polycythemia by cancerous overproduction of EPO is a rare event, but most frequently seen in patients with renal cell carcinoma (RCC). The majority of clear cell RCC displays a strong activation of the transcription factor regulating EPO, the Hypoxia-inducible Factor (HIF). Therefore, it is unclear why only a small minority of patients develop polycythemia. We studied 70 RCC for EPO gene and HIF alpha isoform expression. 34% of all RCC showed expression of EPO mRNA in RNase protection assays, which were almost exclusively of the clear cell type. Only I patient presented with polycythemia. In situ hybridisation revealed that expression of EPO was in the tumour cells. Expression of EPO mRNA was always associated with activation of HIF, which could involve HIF-1 alpha and/or HIF-2 alpha. The frequency of EPO gene expression in RCC is therefore much higher than the prevalence of polycythemia. Furthermore, activation of HIF appears necessary for EPO gene expression in RCC, but is clearly not the only determinant. Further to the reported expression of EPO receptors in tumour tissues, the finding of widespread expression of EPO in RCC supports the recent notion of an involvement of this system in paracrine or autocrine effects of tumour cells. (C) 2007 Wiley-Liss, Inc.