Validation of HB-EGF and amphiregulin as targets for human cancer therapy
Validation of HB-EGF and amphiregulin as targets for human cancer therapy
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DOI：
10.1016/j.bbrc.2007.11.015
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发表时间：
2008-01-18
影响因子：
3.1
通讯作者：
Miyamoto, Shingo
中科院分区：
文献类型：
--
作者：
Yotsumoto, Fusanorl;Yagi, Hiroshi;Miyamoto, Shingo
表皮生长因子受体（EGFR）及其同源配体的异常表达水平已被认为是癌症进展的原因之一。为了研究EGFR配体作为肿瘤治疗靶点的有效性，我们检测了EGFR配体在各种癌细胞中的表达以及小干扰RNA （siRNA）对EGFR配体的体外抗肿瘤作用。HB-EGF主要在卵巢癌、胃癌、乳腺癌、黑色素瘤和胶质母细胞瘤细胞中表达升高，而amphiregulin主要在胰腺癌、结肠癌、前列腺癌、肾细胞癌和胆管癌细胞中表达。将HB-EGF或双调节蛋白sirna转染到这些细胞中，凋亡细胞数量显著增加，EGFR和ERK活化减弱。在肺癌细胞中，没有任何EGFR配体被认为是癌症治疗的有效靶标。这些结果表明HB-EGF和双调节蛋白是癌症治疗的有希望的靶点。(c) 2007爱思唯尔公司版权所有。
Aberrant expression levels of epidermal growth factor receptor (EGFR) and its cognate ligands have been recognized as one of the causes of cancer progression. To investigate the validity of EGFR ligands as targets for cancer therapy, we examined the expression of EGFR ligands and in vitro anti-tumor effects of small interference RNA (siRNA) for EGFR ligands in various cancer cells. HB-EGF expression was dominantly elevated in ovarian, gastric, and breast cancer, melanoma and glioblastoma cells, whereas amphiregulin was primarily expressed in pancreatic, colon, and prostate cancer, renal cell carcinoma and cholangiocarcinoma cells. Transfection of siRNAs for HB-EGF or amphiregulin into these cells significantly increased the numbers of apoptotic cells with attenuation of EGFR and ERK activation. In lung cancer cells, any EGFR ligand was not recognized as a validated target for cancer therapy. These results suggest that HB-EGF and amphiregulin are promising targets for cancer therapy. (c) 2007 Elsevier Inc. All rights reserved.