Potential prognostic biomarker CD73 regulates epidermal growth factor receptor expression in human breast cancer
Potential prognostic biomarker CD73 regulates epidermal growth factor receptor expression in human breast cancer
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潜在的预后生物标志物 CD73 调节人乳腺癌中表皮生长因子受体的表达
DOI：
10.1002/iub.1086
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发表时间：
2012-11-01
期刊：
影响因子：
4.6
通讯作者：
Zhou, Ping
中科院分区：
文献类型：
--
作者：
Zhi, Xiuling;Wang, Yingjian;Zhou, Ping
CD73是一种在乳腺癌细胞中过表达的胞外酶，催化单磷酸腺苷脱磷酸化为腺苷。抗CD73在体内和体外均减缓乳腺癌生长及其扩散。在这项研究中，我们调查了CD73表皮生长因子受体（EGFR）表达的组织芯片和乳腺癌细胞系。在体内和体外实验中，CD73表达与EGFR表达呈正相关（n = 80，r = 0.425，P < 0.01）。用抑制剂或小的shRNA抑制CD73可降低EGFR表达，腺苷和腺苷A2受体激动剂（NECA）可逆转这种作用，提示腺苷参与了CD73对EGFR表达的调控（P < 0.01）。我们还发现CD73通过Src调节EGFR磷酸化（P < 0.01）。通过转录因子（TF）测定，发现CD 73调节一些相关的TF活性，如PPAR？，它介导EGFR的表达，但是否PPAR？CD73介导EGFR表达的作用有待进一步研究。CD73的KaplanMeier无复发生存曲线也在www.kmplot.com中绘制。曲线显示，在雌激素受体阴性的癌症中，CD73表达将病例区分为显著不同的预后组（P < 0.01）。我们的研究结果表明，CD73可能是一个潜在的预后生物标志物与EGFR在人类乳腺癌的共表达。(c)2012年IUBMB。IUBMB Life，64（11）：911920，2012
CD73, an ecto-enzyme overexpressed in breast-cancer cells, catalyzes the dephosphorylation of adenosine monophosphates into adenosine. Anti-CD73 slows breast cancer growth and its spread both in vivo and in vitro. In this study, we investigated the relation of CD73 to epidermal growth factor receptor (EGFR) expression using tissue array and breast cancer cell lines. We found that CD73 expression correlated positively to EGFR expression in vivo (n = 80, r = 0.425, P < 0.01) and in vitro. EGFR expression can be decreased by suppressing CD73 with an inhibitor or small shRNA, and this effect was reversed by adenosine and NECA (adenosine A2 receptor agonist), which suggested that adenosine is involved in EGFR expression regulated by CD73 (P < 0.01). We also showed that CD73 regulates EGFR phosphorylation by Src (P < 0.01). By transcription factor (TF) assay, CD73 was found to regulate some associated TFs activity such as PPAR?, which mediates EGFR expression, although whether PPAR? mediates the effect of CD73 on EGFR expression needs further study. The KaplanMeier recurrence-free survival curves for CD73 were also plotted in www.kmplot.com. The curves show that CD73 expression separates the cases into significantly different prognostic groups among the estrogen receptor-negative cancers (P < 0.01). Our results suggest that CD73 may be a potential prognostic biomarker associated with coexpression of EGFR in human breast cancer. (c) 2012 IUBMB. IUBMB Life, 64(11): 911920, 2012