Expression of hypoxia-inducible genes in tumor cells
Expression of hypoxia-inducible genes in tumor cells
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DOI：
10.1007/s004320050175
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发表时间：
1998-06-01
影响因子：
3.6
通讯作者：
Schwarz, M
中科院分区：
文献类型：
--
作者：
Kress, S;Stein, A;Schwarz, M
肿瘤组织氧合对癌细胞增殖及其对放化疗敏感性的影响。在低氧条件下，哺乳动物细胞表现出适应性反应，导致许多在氧气供应和能量维持中具有明确作用的基因被诱导，例如编码糖酵解途径酶的基因。缺氧诱导因子1 （HIF-1）是一种由HIF-1 α和HIF-1 β两种蛋白组成的转录因子，在低氧条件下观察到的多效性反应中起主要作用。通过Northern分析，我们确定了HIF-1 α和两种已知由HIF-1转录激活的糖酵解酶的mRNA水平，即磷酸甘油酸激酶1 （pgk1）和丙酮酸激酶M2 (PKM2)，在不同的肝癌细胞系和小鼠和人体组织中。缺氧处理各种小鼠和人肝癌细胞系导致PGK1和PKM2 mRNA的数量增加，而HIF-1 α。mRNA水平无显著升高。对小鼠肝脏肿瘤的分析显示，HIF-1 α或PGK1 mRNA水平没有肿瘤特异性升高。在研究的8种人类结直肠癌中，有5种与相应的正常组织相比，PGK1和PKM2 mRNA水平升高，而HIF-1 α mRNA水平没有显著变化。大多数结直肠癌表现出p53免疫反应性，可能是由于基因突变；然而，p53染色模式与糖酵解酶mRNA表达水平无相关性。
Tumor tissue oxygenation impacts on proliferation of cancer cells and their sensitivity towards radio- and chemotherapy. Under low oxygen, mammalian cells show an adaptive response that leads to the induction of a number of genes with well-defined roles in oxygen supply and energy maintenance, e.g. genes encoding enzymes of the glycolytic pathway. The hypoxia-inducible factor 1 (HIF-1), a transcription factor consisting of the two proteins HIF-1 alpha and HIF-1 beta, plays a major role in the pleiotropic response observed under low oxygen. We have determined, by Northern analysis, the mRNA levels of HIF-1 alpha and of two glycolytic enzymes known to be transcriptionally activated by HIF-1, namely phosphoglycerate kinase 1 (PGK 1) and pyruvate kinase M2 (PKM2), in different hepatoma cell lines and in mouse and human tissues. Hypoxic treatment of various mouse and human hepatoma cell lines led to the expected increase in the amount of PGK1 and PKM2 mRNA, while HIF-1 alpha. mRNA levels were not significantly elevated. Analysis of mouse liver tumors demonstrated no tumor-specific increases in HIF-1 alpha or PGK1 mRNA levels. In five of eight human colorectal cancers investigated, PGK1 and PKM2 mRNA levels were increased in comparison to the corresponding normal tissues, while HIF-1 alpha mRNA levels were not significantly changed. The majority of the colorectal cancers demonstrated p53 immunoreactivity, presumably due to mutation of the gene; there was, however, no correlation between the p53 staining pattern and mRNA expression levels of glycolytic enzymes.