Expression of eIF4E during head and neck tumorigenesis: Possible role in angiogenesis
Expression of eIF4E during head and neck tumorigenesis: Possible role in angiogenesis
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DOI：
10.1097/00005537-199908000-00013
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发表时间：
1999-08-01
期刊：
影响因子：
2.6
通讯作者：
Stucker, FJ
中科院分区：
文献类型：
--
作者：
Nathan, CAO;Franklin, S;Stucker, FJ
摘要目的:翻译起始因子eIF4E （4E）在哺乳动物细胞中过表达导致其癌性转化，4E通过选择性地增强其翻译促进两种强大的肿瘤血管生成因子（VEGF和FGF-2）的合成，4E不仅在所有头颈部鳞状细胞癌中过表达，而且在一些发育不良边缘也过表达，头颈部肿瘤的发生是一个多步骤的过程，在此之前有临床明显的癌前病变。分子事件是组织变化的基础；预示着转变。我们想研究4E在肿瘤发生中的作用，并进一步阐明其在血管生成中的因果作用。方法：对115例代表恶性肿瘤组织学进展不同阶段的头颈部标本进行了4E、VEGF和basic (b)-FGF抗体的免疫组织化学分析。这与使用因子VIII的平均血管密度（MVD）相关。结果：增生及低度不典型增生41例，高等级不典型增生40例，癌变34例，低度不典型增生经肿瘤表达4E的比例明显增加。然而，VEGF和b-FGF仅在肿瘤组和发育不良组之间有显著升高，而在低级别和高级别发育不良组之间无显著升高。MVD显著增加，从低（10.7 +/- 1）到高级别发育不良（18.0 +/- 2.3），这种增加在4E阳性病例中更为显著。结论：4E升高与头颈部细胞的进行性转化有关。它与VEGF， b-FGF和MVD的相关性增强了它在血管生成中的可能作用。
Objective: The translation initiation factor eIF4E (4E) when overexpressed in mammalian cells results in their oncogenic transformation, 4E facilitates the synthesis of two powerful tumor angiogenic factors (VEGF and FGF-2) by selectively enhancing their translation, 4E is overexpressed not only in all head and neck squamous cell cancers but also in some dysplastic margins, Tumorigenesis in the head and neck is proposed to be a multistep process preceded by clinically evident precancerous lesions, Molecular events underlie the histological changes that;herald transformation. We wanted to study the role of 4E in tumorigenesis and further elucidate its causal role in angiogenesis, Methods: An immunohistochemical analysis with antibodies to 4E, VEGF, and basic (b)-FGF was performed on 115 specimens of the head and neck representing various stages of histological progression of malignancy. This was correlated with mean vessel density (MVD) using factor VIII. Results: There were 41 cases of hyperplasia and low-grade dysplasia, 40 cases of high-grade dysplasia and 34 cases of cancer, There was a significant increase in the percent of cases expressing 4E from low-grade dysplasia through tumor. However, for VEGF and b-FGF the significant increase was only seen between the tumor group and dysplastic groups and no significant increase was noted between low-grade and high-grade dysplasia. There was a significant increase in MVD from low- (10.7 +/- 1) to high-grade grade dysplasia (18.0 +/- 2.3), This increase was even more striking for the 4E positive cases. Conclusion: 4E elevation is correlated with progressive cell transformation in the head and neck. Its correlation with VEGF, b-FGF, and MVD potentates its possible role in angiogenesis.