Proline-rich tyrosine kinase 2 and its phosphorylated form pY881 are novel prognostic markers for non-small-cell lung cancer progression and patients' overall survival.
Proline-rich tyrosine kinase 2 and its phosphorylated form pY881 are novel prognostic markers for non-small-cell lung cancer progression and patients' overall survival.
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富含脯氨酸的酪氨酸激酶 2 及其磷酸化形式 pY881 是非小细胞肺癌进展和患者总体生存的新型预后标志物。
DOI：
10.1038/bjc.2013.439
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发表时间：
2013-09-03
影响因子：
8.8
通讯作者：
Zhang, X.
中科院分区：
文献类型：
--
作者：
Kuang, B-H;Zhang, M-Q;Xu, L-H;Hu, L-J;Wang, H-B;Zhao, W-F;Du, Y.;Zhang, X.
我们以前的研究表明，富含脯氨酸的酪氨酸激酶2（Pyk 2）在肺癌细胞的锚定非依赖性生长和抗失巢凋亡。本研究旨在探讨Pyk 2及其磷酸化形式在非小细胞肺癌（NSCLC）中的表达及其临床意义。Pyk 2或癌症干细胞标志物（ALDH 1a 1、ABCG 2和Bmi-1）的mRNA和蛋白质水平通过逆转录PCR或蛋白质印迹法进行检测。采用免疫组化（IHC）法检测128例NSCLC中Pyk 2及其磷酸化形式的表达。肺癌组织中Pyk 2 mRNA、总蛋白及其磷酸化形式pY 881的表达水平均高于配对的非癌组织。免疫组化分析显示Pyk 2和Pyk 2 [pY 881]蛋白分别在70例（54.7%）和77例（60.2%）病例中高表达。Pyk 2和Pyk 2 [pY 881]均为NSCLC患者的独立预后因素。Pyk 2功能的获得和丧失研究表明，Pyk 2能够上调ALDH 1a 1、ABCG 2和Bmi-1的表达，并增强A549和H460细胞软琼脂集落形成能力。Pyk 2和磷酸化Pyk 2 [pY 881]都是NSCLC的潜在预后因子和治疗靶点。
Our previous study revealed that proline-rich tyrosine kinase 2 (Pyk2) is implicated in both anchorage-independent growth and anoikis resistance in lung cancer cells. This study aims to explore the expression and clinical significance of Pyk2 and its phosphorylated forms in non-small-cell lung cancer (NSCLC). The mRNA and protein levels of Pyk2 or cancer stem cell markers (ALDH1a1, ABCG2 and Bmi-1) were either examined by reverse transcription–PCR or western blotting. An immunohistochemistry (IHC) assay was conducted to analyse the expression of Pyk2 and its phosphorylated forms in 128 NSCLC cases. The levels of Pyk2 mRNA, total protein, and its phosphorylated form pY881 were higher in lung cancer lesions than in the paired noncancerous tissues. The IHC analysis showed the levels of the Pyk2 and Pyk2[pY881] proteins were highly expressed in 70 (54.7%) and 77 (60.2%) cases, respectively. Both Pyk2 and Pyk2[pY881] were independent prognostic factors for NSCLC patients. The gain and loss study of Pyk2 function revealed that Pyk2 could upregulate the expression of ALDH1a1, ABCG2 and Bmi-1 and enhance the ability of colony formation in soft agar assay in A549 and H460 cells. Both Pyk2 and phosphorylated Pyk2[pY881] are potential prognostic factors and therapeutic targets for NSCLC.
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影响因子：
7.8
作者：
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通讯作者：
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