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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生存期的新型预后标志物。

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.

机构信息

State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 East Dongfeng Road, Guangzhou 510060, China.

出版信息

Br J Cancer. 2013 Sep 3;109(5):1252-63. doi: 10.1038/bjc.2013.439. Epub 2013 Aug 6.

DOI:10.1038/bjc.2013.439
PMID:23922106
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3778294/
Abstract

BACKGROUND

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).

METHODS

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.

RESULTS

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.

CONCLUSION

Both Pyk2 and phosphorylated Pyk2[pY881] are potential prognostic factors and therapeutic targets for NSCLC.

摘要

背景

我们之前的研究表明富含脯氨酸的酪氨酸激酶 2（Pyk2）参与肺癌细胞的非锚定依赖性生长和抗失巢凋亡。本研究旨在探讨 Pyk2 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。

方法

通过逆转录-PCR 或 Western blot 检测 Pyk2 或癌症干细胞标志物（ALDH1a1、ABCG2 和 Bmi-1）的 mRNA 和蛋白水平。免疫组织化学（IHC）检测 128 例 NSCLC 病例中 Pyk2 及其磷酸化形式的表达。

结果

肺癌病变中 Pyk2 mRNA、总蛋白及其磷酸化形式 pY881 的水平均高于配对的非癌组织。IHC 分析显示 Pyk2 和 Pyk2[pY881]蛋白的水平在 70 例（54.7%）和 77 例（60.2%）病例中高度表达。Pyk2 和 Pyk2[pY881]均是非小细胞肺癌患者的独立预后因素。Pyk2 功能的获得和缺失研究表明，Pyk2 可以上调 A549 和 H460 细胞中 ALDH1a1、ABCG2 和 Bmi-1 的表达，并增强软琼脂克隆形成能力。

结论

Pyk2 和磷酸化 Pyk2[pY881]均是非小细胞肺癌的潜在预后因素和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/185d/3778294/17a641ac81b7/bjc2013439f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/185d/3778294/9c161a31e69c/bjc2013439f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/185d/3778294/17a641ac81b7/bjc2013439f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/185d/3778294/26ff5779c225/bjc2013439f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/185d/3778294/a86cfd694b99/bjc2013439f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/185d/3778294/be4e21e62e7f/bjc2013439f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/185d/3778294/d1d4cf6bde41/bjc2013439f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/185d/3778294/6d8b7352c5bd/bjc2013439f5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/185d/3778294/17a641ac81b7/bjc2013439f7.jpg

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