Translation initiation factor eIF-4gamma is encoded by an amplified gene and induces an immune response in squamous cell lung carcinoma
Translation initiation factor eIF-4gamma is encoded by an amplified gene and induces an immune response in squamous cell lung carcinoma
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DOI：
10.1093/hmg/6.1.33
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发表时间：
1997-01-01
影响因子：
3.5
通讯作者：
Meese, E
中科院分区：
文献类型：
--
作者：
Brass, N;Heckel, D;Meese, E
细胞癌基因的扩增是人类癌症中基因表达改变的重要机制，使用比较基因组杂交，我们最近在30%的肺鳞状细胞癌中发现了3q26.1-q26.3的扩增，包括微解剖介导的程序在内的各种方法允许克隆扩增区域内编码的基因，但不能直接导致生物学相关基因的鉴定。在本研究中，我们通过结合免疫学和分子遗传学的方法来分析鳞状细胞肺癌，为了鉴定扩增的和肿瘤相关的基因，我们从一个3q扩增的肿瘤中生成cDNA表达文库，并将表达的重组多肽与自体血清杂交，在40万个cDNA克隆中，我们鉴定出17个抗原，诱导鳞状细胞肺癌患者的免疫反应。虽然大多数克隆代表单个基因，但序列分析显示，17个cdna中有4个与最近分配在3q上的真核翻译起始因子(eIF)-4gamma基因几乎相同，我们证明了eIF-4gamma基因在独立鳞状细胞肺癌的3q26-q27内扩增。在本研究中，我们报告了几种抗原的鉴定，这些抗原在鳞状细胞肺癌患者中引起免疫反应，包括eIF-4gamma，eif - 4γ由一个扩增基因编码，可能在鳞状细胞肺癌的发展中起着至关重要的作用。
Amplification of cellular oncogenes is an important mechanism of altered gene expression in human cancers, Using comparative genomic hybridization we recently identified an amplification at 3q26.1-q26.3 in 30% of squamous cell carcinomas of the lung, A variety of methods including microdissection-mediated procedures permit cloning of genes encoded within amplified domains but do not directly lead to the identification of biologically relevant genes. In this study, we have circumvented this problem by combining an immunological and molecular genetic approach to analyze squamous cell lung carcinoma, To identify both amplified and tumor relevant genes, we generated a cDNA expression library from a tumor with the 3q amplification and hybridized the expressed recombinant polypeptides with the autologous serum, Of 400 000 cDNA clones we identified 17 antigens which induce an immune response in a patient with squamous cell lung carcinoma, While most clones represent individual genes sequence analysis revealed that four of the 17 cDNAs are nearly identical with the eukaryotic translation initiation factor (eIF)-4gamma recently assigned on 3q, We demonstrated that the gene for eIF-4gamma was amplified within 3q26-q27 in independent squamous cell lung carcinomas, In this study, we report the identification of several antigens which elicit an immune response in a squamous cell lung carcinoma patient including eIF-4gamma, eIF-4gamma is encoded by an amplified gene and possibly plays a crucial part in the development of squamous cell lung carcinoma.