Plasma protein kinase C (PKC)α as a biomarker for the diagnosis of cancers
Plasma protein kinase C (PKC)α as a biomarker for the diagnosis of cancers
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DOI：
10.1093/carcin/bgp210
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发表时间：
2009-11-01
期刊：
影响因子：
4.7
通讯作者：
Katayama, Yoshiki
中科院分区：
文献类型：
--
作者：
Kang, Jeong-Hun;Asai, Daisuke;Katayama, Yoshiki
蛋白激酶C (PKC) α在癌细胞的分化、增殖和凋亡中起关键作用，其活性在癌细胞中高于正常细胞。在本研究中，我们探讨了血浆中活化PKC α的存在及其在癌症诊断中的可能性。血浆样本分别取自移植瘤小鼠模型和正常小鼠。通过基质辅助激光解吸/电离飞行时间质谱分析PKC α特异性肽底物（Alphatomega）的磷酸化比率，并通过western blot分析鉴定活化的PKC α。与对照小鼠相比，在患癌小鼠（U87、A549、A431、HuH-7和B16黑色素瘤）的血浆中发现活化PKC α水平升高。肽底物的磷酸化比率随着肿瘤大小的增加而增加。此外，加入高度特异性的PKC α抑制剂Ro-31-7549可以产生浓度依赖性的磷酸化比率降低，而非PKC α抑制剂rottlerin和H-89对磷酸化比率没有显著影响。此外，激活的PKC α水平在癌症切除后降低，但在癌症复发时升高。根据这些结果，我们建议(i)血浆中活化的PKC α可以作为癌症诊断的有用生物标志物；（ii）可以监测活化的PKC α水平，以评估手术切除后癌症的复发。据我们所知，这是第一份证明血浆中活化PKC α存在及其在癌症诊断中的可能性的报告。
Protein kinase C (PKC)alpha plays a key role in the differentiation, proliferation and apoptosis of cancer cells, and its activity is higher in cancer cells than in normal cells. In the present study, we investigated the existence of activated PKC alpha in plasma and its possibility for cancer diagnosis. Plasma samples were prepared from xenograft mouse models of cancer and from normal mice. Phosphorylation ratios for a PKC alpha-specific peptide substrate (Alphatomega) were analyzed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry and activated PKC alpha was identified by western blot analysis. Increased levels of activated PKC alpha were found in the plasma of cancer-bearing mice (U87, A549, A431, HuH-7 and B16 melanoma) compared with the levels found in control mice. Phosphorylation ratios for peptide substrate increased with an increase in tumor size. Moreover, the addition of Ro-31-7549, a highly specific inhibitor of PKC alpha, produced a concentration-dependent reduction of phosphorylation ratios, whereas the non-PKC alpha inhibitors, rottlerin and H-89, did not significantly effect phosphorylation ratios. In addition, the level of activated PKC alpha decreased after cancer resection but increased if the cancer recurred. From these results, we suggest that (i) activated PKC alpha in plasma can be a useful biomarker for the diagnosis of cancers and (ii) the level of activated PKC alpha can be monitored to assess the recurrence of cancer after surgical removal. To our knowledge, this is the first report demonstrating the existence of activated PKC alpha in plasma and its possibility for cancer diagnosis.