Joseph Pius, O'Kernick Christina M, Othumpangat Sreekumar, Lei Yi-Xiong, Yuan Bao-Zhu, Ong Tong-Man
Molecular Carcinogenesis Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA.
Mol Carcinog. 2004 Jul;40(3):171-9. doi: 10.1002/mc.20033.
Several studies have demonstrated the overexpression of certain eukaryotic translation factors in human cancer cell lines and in malignant tissues. In this study, with human cancer cell lines derived from lungs, breast, prostate, and skin, we have examined the expression profile of 36 translation factors consisting of 27 initiation factors, 8 elongation factors, and 1 termination factor. Translation initiation factors 2C2 and 4E1 and translation elongation factors 1A2 and 1delta were found overexpressed (2- to 2000-fold) in many of the cancer cell lines compared to their corresponding normal cell lines. Among the translation factors analyzed, translation elongation factor 1A2 exhibited the most significant alteration in expression: 10- to 2000-fold overexpression was noticed in nine out of ten cancer cell lines analyzed. Whether the overexpression of translation elongation factor 1A2 can be used as a potential tumor marker was tested with the cancer profiling array (BD Biosciences, Palo Alto, CA) consisting of 241 paired cDNA samples generated from 13 different cancer/noncancer tissue types. Overexpression of translation elongation factor 1A2 was noticed in several tumor tissue samples, most notably in the human colon cancer samples which exhibited at least a twofold overexpression among 35% of the samples analyzed. Besides colon, tumor samples derived from lungs, kidney, rectum, and ovary also exhibited more than a twofold overexpression of translation elongation factor 1A2 in at least 20% of the samples analyzed. These results indicate that human carcinogenesis is often associated with alterations in the expression of various translation factors especially the overexpression of eukaryotic translation elongation factor 1A2.
多项研究已证实在人类癌细胞系和恶性组织中某些真核生物翻译因子存在过表达。在本研究中，我们利用源自肺、乳腺、前列腺和皮肤的人类癌细胞系，检测了由27种起始因子、8种延伸因子和1种终止因子组成的36种翻译因子的表达谱。与相应的正常细胞系相比，发现翻译起始因子2C2和4E1以及翻译延伸因子1A2和1δ在许多癌细胞系中过表达（2至2000倍）。在所分析的翻译因子中，翻译延伸因子1A2的表达变化最为显著：在分析的十个癌细胞系中有九个出现了10至2000倍的过表达。利用由13种不同癌症/非癌症组织类型产生的241对cDNA样本组成的癌症分析阵列（BD生物科学公司，加利福尼亚州帕洛阿尔托），测试了翻译延伸因子1A2的过表达是否可作为一种潜在的肿瘤标志物。在几个肿瘤组织样本中发现了翻译延伸因子1A2的过表达，最显著的是在人类结肠癌样本中，在所分析的35%的样本中至少有两倍的过表达。除了结肠，源自肺、肾、直肠和卵巢的肿瘤样本在至少20%的分析样本中也表现出翻译延伸因子1A2超过两倍的过表达。这些结果表明，人类致癌作用通常与各种翻译因子表达的改变有关，尤其是真核生物翻译延伸因子1A2的过表达。
