Analysis of the c-rtbB-2 and EGFR, and the ir downstream signal transduction system.

本文研究了28例肺癌组织中EGFR的扩增、突变和活化与其与Stat-3、Akt和ERK1/2的相关性。在5例<EGFR</>扩增的病例中，EGFR的表达和磷酸化水平均较高，且Stat-3被激活。5例检测到点突变，其中EGFR表达和磷酸化增强，4例Akt被激活。在其余19例中，4例EGFR蛋白表达上调和磷酸化，但EGFR表达或激活与特定下游分子的激活无关。然而，Stat-3或Akt，而不是两者，是相互和互补激活的。这些结果表明，通过基因扩增，Stat-3的激活是过度表达的EGFR下游的一个关键事件。相反，具有<i>EGFR</i>突变的肿瘤细胞可能持续激活Akt级联。最后，在大多数无表皮生长因子受体异常的病例中，I…更多的TS下游分子以相互和互补的方式发挥作用。目前的数据可能为肺癌的潜在化疗方案提供新的见解，包括Stat-3和Akt的抑制剂。我们在29例骨/软组织肿瘤(BSTT)中研究了EGFR异常和蛋白激活之间的相关性。免疫组织化学检测发现22.6%的肉瘤组织中有EGFR过表达。免疫印迹显示，在EGFR表达上调的肉瘤中，47.4%的肉瘤组织中有EGFR激活。在2例EGFR拷贝数高的MFH中，EGFR的表达和磷酸化水平显著升高，并激活了Stat-3。3例检测到错义突变，2例发现EGFR和Stat-3的激活。在其他病例中，在肉瘤和良性病变中均发现EGFR表达上调，但仅在肉瘤中发现激活。在3个下游级联中，Akt通路被激活的频率高于Stat-3或Erkl/2。Stat-3在表现为上皮性的肿瘤中被激活。这些结果表明，Stat-3的激活可能是高水平的EGFR拷贝过表达的EGFR下游的一个关键事件。相反，EGFR突变不一定激活特定的下游级联反应。这些结果表明，EGFR介导的级联反应是BSTT特定亚群的分子靶向治疗的候选对象。较少

The correlations among <I>EGFR</I> amplification, mutation, and activation of EGFR, Stat-3, Akt and Erk1/2 were investigated in 28 cases of human lung carcinomas. In 5 cases with <I>EGFR</I> amplification, EGFR expression and phosphorylation levels were higher, and Stat-3 was activated. Point mutations were detected in 5 cases, in which EGFR expression and phosphorylation were enhanced, and Akt was activated in 4 cases. In the remaining 19 cases, EGFR protein expression was upregulated and phosphorylated in 4 cases, but neither EGFR expression nor activation correlated with activation of particular downstream molecules. However, either Stat-3 or Akt, but not both, was activated reciprocally and complementarily. These results suggest that Stat-3 activation is a critical event downstream of overexpressed EGFR by gene amplifica tion. In contrast, tumor cells with <I>EGFR</I> mutation may persistently activate Akt-cascade. Finally, in the majority of cases without <I>EGFR</I> aberration, i … More ts downstream molecules function in reciprocal and complementary manner. The current data could provide novel insights into potential chemotherapeutic regimens for lung carcinomas, including inhibitors of Stat-3, Akt Correlations among EGFR aberrations and activation of proteins were investigated in 29 cases of bone/soft tissue tumors (BSTTs). By immunohistochemistry, EGFR overexpression was found in 22.6% of sarcomas. By immunoblotting, among sarcoma cases showing upregulation of EGFR, 47.4% showed EGFR activation. In 2 cases of MFH, with high level of EGFR copies, EGFR expression and phosphorylation levels were significantly higher, and Stat-3 was activated. Missense mutations were detected in 3 cases, and activation of EGFR and Stat-3 were found in 2 cases. In other cases, upregulation of the EGFR was found in both sarcomas and benign lesions, but activation was found only in sarcomas. Among the 3 downstream cascades, Akt pathway was most frequently activated than those of Stat-3 or Erkl/2,. and Stat-3 was activated in tumors exhibiting epithelial nature. These results suggest that Stat-3 activation may be a critical event downstream of overexpressed EGFR by high level EGFR copies. In contrast, EGFR mutation may not necessarily activate specific downstream cascades. These results suggest that EGFR-mediated cascades are candidates for molecular targeting therapy in defined subsets of BSTTs. Less