C35 (C17orf37) is a novel tumor biomarker abundantly expressed in breast cancer
C35 (C17orf37) is a novel tumor biomarker abundantly expressed in breast cancer
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DOI：
10.1158/1535-7163.mct-06-0389
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发表时间：
2006-11-01
影响因子：
5.7
通讯作者：
Zauderer, Maurice
中科院分区：
文献类型：
--
作者：
Evans, Elizabeth E.;Henn, Alicia D.;Zauderer, Maurice
确定共同的肿瘤特异性靶点在开发广泛适用的治疗方法方面是有用的。在一项旨在确定乳腺癌上调基因的研究中，通过对肿瘤和正常乳腺细胞系的代表性差异分析，选择了一个与新基因C35(C17orf37)相对应的cDNA克隆。Northern印迹和实时定量聚合酶链式反应证实C35转录本在肿瘤组织中大量表达。C35基因位于染色体17q12上，距ERBB2癌基因3‘端505个核苷酸，是曲妥珠单抗(Herceptin(TM))治疗的抗原靶点。编码C35和ERBB2基因的染色体排列是尾对尾的。开放阅读框编码一个功能未知的12 kDa蛋白质。免疫组织化学检测到C35蛋白的强健和频繁表达，包括32%的1级和66%的2级和3级浸润性导管癌(相比之下，20%的HER-2/neu过表达)，38%的浸润性小叶癌(典型的HER-2/neu阴性)，以及其他组织中的肿瘤。除睾丸中的间质细胞和少量正常乳腺组织中的微量C35外，C35在38种不同的正常人组织中均未检测到。C35在疾病早期和晚期的表达谱清晰而有利，包括在各种乳腺癌中高表达，在远处转移中大量表达，在正常组织中不表达或低水平表达，值得进一步研究C35作为生物标志物和/或开发广泛适用的癌症特异性治疗的靶点的相关性。
Identification of shared tumor-specific targets is useful in developing broadly applicable therapies. In a study designed to identify genes up-regulated in breast cancer, a cDNA clone corresponding to a novel gene C35 (C17orf37) was selected by representational difference analysis of tumor and normal human mammary cell lines. Abundant expression of C35 transcript in tumors was confirmed by Northern blot and real-time PCR. The C35 gene is located on chromosome 17q12, 505 nucleotides from the 3' end of the ERBB2 oncogene, the antigenic target for trastuzumab (Herceptin (TM)) therapy. The chromosomal arrangement of the genes encoding C35 and ERBB2 is tail to tail. An open reading frame encodes a 12-kDa protein of unknown function. Immunohistochemical analysis detected robust and frequent expression of C35 protein, including 32% of grade 1 and 66% of grades 2 and 3 infiltrating ductal carcinomas of the breast (in contrast to 20% overexpressing HER-2/neu), 38% of infiltrating lobular carcinoma (typically HER-2/neu negative), as well as tumors arising in other tissues. C35 was not detected in 38 different normal human tissues, except Leydig cells in the testes and trace levels in a small percentage of normal breast tissue samples. The distinct and favorable expression profile of C35 spanning early through late stages of disease, including high frequency of overexpression in various breast carcinoma, abundant expression in distant metastases, and either absence or low level expression in normal human tissues, warrants further investigation of the relevance of C35 as a biomarker and/or a target for development of broadly applicable cancer-specific therapies.