Vascular endothelial growth factor and nitric oxide synthase expression in human lung cancer and the relation to p53.
Vascular endothelial growth factor and nitric oxide synthase expression in human lung cancer and the relation to p53.
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DOI：
10.1038/bjc.1998.470
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发表时间：
1998-07
影响因子：
8.8
通讯作者：
Harris, C C
中科院分区：
文献类型：
--
作者：
Ambs, S;Bennett, W P;Merriam, W G;Ogunfusika, M O;Oser, S M;Khan, M A;Jones, R T;Harris, C C
血管内皮生长因子(VEGF)的表达和肿瘤相关基因的突变随着肿瘤的进展而增加。这种相关性提示了癌基因和抑癌基因调节血管内皮生长因子的假说，最近报道了肺癌中P53改变和血管内皮生长因子表达增加之间的显著相关性。为了进一步验证这一假设，我们分析了27例非小细胞肺癌(NSCLC)中VEGF蛋白的表达和p53和K-ras基因的突变：16例鳞状细胞癌，6例腺癌，1例大细胞癌，2例类癌和2例未分化肿瘤。VEGF在50%的鳞癌和类癌中表达，而在其他组织中均不表达。P53基因突变14例(52%)，K-ras基因突变发生在2例腺癌和1例鳞癌中，与血管内皮生长因子表达无关。由于一氧化氮也调节血管生成，我们检测了非小细胞肺癌中一氧化氮合酶的表达。肺癌组织中钙离子依赖性一氧化氮合酶活性明显低于癌旁组织(P<；0.004)。尽管在非肿瘤组织和大多数癌组织中检测不到非钙离子依赖性的NOS活性，表明NOS2的表达，但在三种鳞癌中都有显著的活性。综上所述，我们的数据没有显示在非小细胞肺癌中p53对血管内皮生长因子的直接调节作用。最后，我们没有发现在非小细胞肺癌进展过程中一氧化氮合酶亚型的上调，这已经被认为是妇科和乳腺癌的结果。
Vascular endothelial growth factor (VEGF) expression and mutations of cancer-related genes increase with cancer progression. This correlation suggests the hypothesis that oncogenes and tumour suppressors regulate VEGF, and a significant correlation between p53 alteration and increased VEGF expression in human lung cancer was reported recently. To further examine this hypothesis, we analysed VEGF protein expression and mutations in p53 and K-ras in 27 non-small-cell lung cancers (NSCLC): 16 squamous cell, six adenocarcinomas, one large cell, two carcinoids and two undifferentiated tumours. VEGF was expressed in 50% of the squamous cell carcinomas (SCC) and carcinoids but none of the others. p53 mutations occurred in 14 tumours (52%), and K-ras mutations were found in two adenocarcinomas and one SCC; there was no correlation between the mutations and VEGF expression. As nitric oxide also regulates angiogenesis, we examined NOS expression in NSCLC. The Ca2+-dependent NOS activity, which indicates NOS1 and NOS3 expression, was significantly reduced in lung carcinomas compared with adjacent non-tumour tissue (P < 0.004). Although the Ca2+-independent NOS activity, which indicates NOS2 expression, was low or undetectable in non-tumour tissues and most carcinomas, significant activity occurred in three SCC. In summary, our data do not show a direct regulation of VEGF by p53 in NSCLC. Finally, we did not find the up-regulation of NOS isoforms during NSCLC progression that has been suggested for gynaecological and breast cancers.