Bluemlein Katharina, Grüning Nana-Maria, Feichtinger René G, Lehrach Hans, Kofler Barbara, Ralser Markus
Max Planck Institute for Molecular Genetics, Berlin, Germany.
Oncotarget. 2011 May;2(5):393-400. doi: 10.18632/oncotarget.278.
The Warburg effect describes the circumstance that tumor cells preferentially use glycolysis rather than oxidative phosphorylation for energy production. It has been reported that this metabolic reconfiguration originates from a switch in the expression of alternative splice forms (PKM1 and PKM2) of the glycolytic enzyme pyruvate kinase (PK), which is also important for malignant transformation.However, analytical evidence for this assumption was still lacking. Using mass spectrometry, we performed an absolute quantification of PKM1 and PKM2 splice isoforms in 25 human malignant cancers, 6 benign oncocytomas, tissue matched controls, and several cell lines. PKM2 was the prominent isoform in all analyzed cancer samples and cell lines. However, this PKM2 dominance was not a result of a change in isoform expression, since PKM2 was also the predominant PKM isoform in matched control tissues. In unaffected kidney, lung, liver, and thyroid, PKM2 accounted for a minimum of 93% of total PKM, for 80% - 96% of PKM in colon,and 55% - 61% of PKM in bladder. Similar results were obtained for a panel of tumor and non-transformed cell lines, where PKM2 was the predominant form.Thus, our results reveal that an exchange in PKM1 to PKM2 isoform expression during cancer formation is not occurring, nor do these results support conclusions that PKM2 is specific for proliferating, and PKM1 for non-proliferating tissue.
瓦伯格效应描述了肿瘤细胞优先利用糖酵解而非氧化磷酸化来产生能量的情况。据报道，这种代谢重排源于糖酵解酶丙酮酸激酶（PK）的可变剪接形式（PKM1和PKM2）表达的转变，这对恶性转化也很重要。然而，这一假设仍缺乏分析证据。我们使用质谱法对25种人类恶性肿瘤、6种良性嗜酸性细胞瘤、组织匹配的对照以及几种细胞系中的PKM1和PKM2剪接异构体进行了绝对定量。PKM2是所有分析的癌症样本和细胞系中的主要异构体。然而，这种PKM2的优势并非异构体表达变化的结果，因为PKM2在匹配的对照组织中也是主要的PKM异构体。在未受影响的肾脏、肺、肝脏和甲状腺中，PKM2至少占总PKM的93%，在结肠中占PKM的80% - 96%，在膀胱中占PKM的55% - 61%。对于一组肿瘤和未转化的细胞系也获得了类似的结果，其中PKM2是主要形式。因此，我们的结果表明，在癌症形成过程中并未发生PKM1到PKM2异构体表达的交换，这些结果也不支持PKM2对增殖组织特异而PKM1对非增殖组织特异的结论。
