Selective p38 activation in human non-small cell lung cancer
Selective p38 activation in human non-small cell lung cancer
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DOI：
10.1165/ajrcmb.26.5.4689
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发表时间：
2002-05-01
影响因子：
6.4
通讯作者：
Lee, TC
中科院分区：
文献类型：
--
作者：
Greenberg, AK;Basu, S;Lee, TC
丝裂原活化蛋白激酶（MAPK）途径将信号从细胞膜传递到细胞核。MAPK级联反应的激活可能在恶性转化中发挥作用。我们假设这些通路中的一个或多个的增强表达将发生在人类肺癌中。使用Western印迹分析从切除的非小细胞肺癌和匹配的非肿瘤性肺组织的组织匀浆，我们确定，只有激活的p38在肿瘤中持续增加与正常组织相比。体外激酶试验证实，活化的MAPK的水平与酶的活性相关，免疫组织化学分析证实了活化的MAPK的细胞定位。我们在低氧室中孵育肺癌细胞系以模拟实体肺肿瘤中的低氧环境，但未发现p38激活增加。与我们的预期相反，ERK和JNK，传统上与细胞生长和恶性转化相关的MAPK途径，在人肺肿瘤样品中并没有持续激活。然而，p38，一种通常与应激反应，生长停滞和凋亡相关的MAPK，在所有的人肺癌样本中被激活，这表明该途径在恶性细胞生长或转化中的额外作用。
The mitogen-activated protein kinase (MAPK) pathways transmit signals from the cell membrane to the nucleus. Activation of MAPK cascades may play a role in malignant transformation. We hypothesized that enhanced expression of one or more of these pathways would occur in human lung cancers. Using Western blot analysis of tissue homogenates from resected nonsmall cell lung cancers and matched non-neoplastic lung tissue, we determined that only activated p38 was consistently increased in tumor compared with normal tissue. In vitro kinase assays confirmed that the levels of activated MAPK correlated with the activity of the enzymes, and immunohistochemical analysis confirmed the cellular localization of the activated MAPKs. We incubated a lung cancer cell line in a hypoxic chamber to simulate the hypoxic environment in solid lung tumors, but found no increase in p38 activation. Contrary to our expectations, ERK and JNK, the MAPK pathways traditionally associated with cell growth and perhaps malignant transformation, were not consistently activated in the human lung tumor samples. However, p38, a MAPK usually associated with stress responses, growth arrest, and apoptosis, was activated in all of the human lung cancer samples, suggesting an additional role for this pathway in malignant cell growth or transformation.