STAT3 expression in activating EGFR-driven adenocarcinoma of the lung
STAT3 expression in activating EGFR-driven adenocarcinoma of the lung
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STAT3 表达激活 EGFR 驱动的肺腺癌
DOI：
10.1016/j.lungcan.2011.05.015
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发表时间：
2012
期刊：
影响因子：
5.3
通讯作者：
Kiura Katsuyuki
中科院分区：
文献类型：
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作者：
Takata Saburo;Takigawa Nagio;Segawa Yoshihiko;Kubo Toshio;Ohashi Kadoaki;Kozuki Toshiyuki;Teramoto Norihiro;Yamashita Motohiro;Toyooka Shinichi;Tanimoto Mitsune;Kiura Katsuyuki
细支气管肺泡癌（BAC）型常出现在浸润性腺癌的边缘。我们研究了EGFR信号异常参与腺癌的进展。50例肿瘤来自接受肺腺癌手术的患者，在计算机断层扫描上显示为磨玻璃样阴影的致密区域。分析了直径<1cm、1-2cm和≥2cm的肿瘤分别为6例、18例和26例。肿瘤直径≤2cm的24例中，9例为浸润前病变，15例为浸润性病变。通过免疫组织化学检测，EGFR、pAKT和pMAPK在腺癌中心相对于BAC组分过表达（p<0.01），而pSTAT 3表达逆转（p=0.017）。在直径≤2cm的肿瘤中，浸润前肿瘤中心区域的pSTAT 3表达高于浸润性肿瘤（p=0.005）。在88%的EGFR突变体（n=17）和82%的野生型肿瘤（n=33）的BAC组分中鉴定出pSTAT 3。还研究了表达delE 748-A752 EGFR的转基因小鼠和两种肺癌细胞系（PC-9突变体和A549野生型EGFR）。在转基因小鼠中，pSTAT 3在腺癌中心周围的BAC组分中过表达。过表达pSTAT 3的两种肺癌细胞系对JAK 2/STAT 3抑制剂（JSI-124）同样敏感。STAT 3在腺癌进展中的作用应进一步研究。
Bronchioloalveolar carcinoma (BAC) pattern is often seen at the margin of invasive adenocarcinomas. We investigated EGFR signaling abnormalities involved in the progression of adenocarcinoma. Fifty tumors were obtained from patients who underwent surgery for lung adenocarcinoma seen as dense areas in ground glass opacity on computed tomography. Six, 18, and 26 tumors <1cm, 1–2cm, and ≥2cm in diameter, respectively, were analyzed. Of the 24 tumors ≤2cm in diameter, nine were preinvasive and 15 were invasive. EGFR, pAKT, and pMAPK were overexpressed in the center of the adenocarcinoma compared to the BAC component (p<0.01) by immunohistochemistry, while pSTAT3 expression was reversed (p=0.017). In the tumors ≤2cm in diameter, pSTAT3 expression in the central area was higher in preinvasive tumors than in invasive tumors (p=0.005). pSTAT3 was identified in the BAC component of 88% of the EGFR mutant (n=17) and 82% of the wild-type tumors (n=33). Transgenic mice expressing delE748-A752 EGFR and two lung cancer cell lines (PC-9 mutant and A549 wild-type EGFR) were also investigated. In transgenic mice, pSTAT3 was overexpressed in the BAC component around the adenocarcinoma center. Two lung cancer cell lines that overexpressed pSTAT3 were equally sensitive to a JAK2/STAT3 inhibitor (JSI-124). The role of STAT3 in the progression of adenocarcinoma should be further pursued.