Rosenwald I B, Hutzler M J, Wang S, Savas L, Fraire A E
Department of Pathology, University of Massachusetts Memorial Health Care, Worcester, Massachusetts, USA.
Cancer. 2001 Oct 15;92(8):2164-71. doi: 10.1002/1097-0142(20011015)92:8<2164::aid-cncr1559>3.0.co;2-a.
When resting cells are stimulated by growth factors, an increase in protein synthesis follows that depends in part on two key eukaryotic translation initiation factors, 4E and 2alpha (eIF-4E and eIF-2alpha, respectively). In the normal cell, expression and activity of both factors are increased transiently, whereas they become elevated constitutively in oncogene-transformed cultured cells, and overexpression of either initiation factor in rodent cells makes them tumorigenic. In this study, the authors investigated an association between the expression of these translation initiation factors and lung carcinogenesis.
The authors analyzed the expression of the protein synthesis initiation factors eIF-4E and eIF-2alpha by immunohistochemistry in bronchioloalveolar (BA) and squamous cell (SC) carcinomas of the lung. Western blot analysis was performed to validate the specificity of antibodies in detecting their cognate proteins.
Both eIF-4E and eIF-2alpha were increased frequently in BA carcinomas, whereas only rarely did SC carcinomas demonstrate elevation of these translation initiation factors. An analysis of cyclin D1 expression did not show a strict correlation with the expression of eIF-4E and eIF-2alpha.
Increased expression of either one or both translation initiation factors may facilitate accelerated growth and division of neoplastic cells in BA carcinoma of the lung. However, the current findings suggest a possibility that increased cell growth and proliferation in SC carcinoma may be achieved through a mechanism independent of increases in eIF-4E and eIF-2alpha expression.
当静止细胞受到生长因子刺激时,蛋白质合成会增加,这部分依赖于两个关键的真核生物翻译起始因子,即4E和2α(分别为eIF - 4E和eIF - 2α)。在正常细胞中,这两种因子的表达和活性会短暂增加,而在癌基因转化的培养细胞中它们会持续升高,并且在啮齿动物细胞中任一翻译起始因子的过表达都会使其具有致瘤性。在本研究中,作者调查了这些翻译起始因子的表达与肺癌发生之间的关联。
作者通过免疫组织化学分析了肺细支气管肺泡癌(BA)和肺鳞状细胞癌(SC)中蛋白质合成起始因子eIF - 4E和eIF - 2α的表达。进行蛋白质印迹分析以验证抗体检测其同源蛋白的特异性。
eIF - 4E和eIF - 2α在BA癌中经常升高,而SC癌中这些翻译起始因子仅很少升高。细胞周期蛋白D1表达分析未显示与eIF - 4E和eIF - 2α的表达有严格相关性。
一种或两种翻译起始因子表达增加可能促进肺BA癌中肿瘤细胞的加速生长和分裂。然而,目前的研究结果提示,SC癌中细胞生长和增殖增加可能是通过一种独立于eIF -