Stat3 downstream genes serve as biomarkers in human lung carcinomas and chronic obstructive pulmonary disease.
Stat3 downstream genes serve as biomarkers in human lung carcinomas and chronic obstructive pulmonary disease.
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DOI：
10.1016/j.lungcan.2008.05.025
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发表时间：
2009-03
期刊：
影响因子：
5.3
通讯作者：
Yan, Cong
中科院分区：
文献类型：
--
作者：
Qu, Peng;Roberts, Jennifer;Li, Yuan;Albrecht, Marjorie;Cummings, Oscar W.;John, N. Eble;Du, Hong;Yan, Cong
吸烟会导致肺癌和慢性阻塞性肺疾病(COPD)，给人类带来严重的健康问题。这两种疾病是相互关联的，都可以由肺部的慢性炎症引起。为了探讨肺癌形成的分子机制，最近建立了CCSP-RTTA/(Teto)7Stat3C双转基因模型。在该模型中，STAT3信号通路的持续激活导致肺部炎症和肺腺癌的形成。通过Affymetrix基因芯片芯片分析鉴定出一组STAT3下游基因，可作为肺癌诊断和预后的生物标志物。为了确定哪些人类肺癌与STAT3途径相关，在人类肺癌(腺癌和鳞癌)和COPD肺组织中筛选了多个STAT3下游基因。在癌症和COPD中，STAT3基因上调。在小鼠中，一组STAT3上调的下游基因在人类腺癌中上调，但在人类鳞癌中不上调。这组基因在有吸烟史的COPD患者的肺组织中也略有上调，而在没有吸烟史的患者中没有上调。一些STAT3下调的下游基因在癌症和COPD中也显示出不同的表达模式。这些研究支持这样一个概念，即STAT3是一种强大的致癌分子，在小鼠和人类肺腺癌的形成中发挥作用。在体内，腺癌和鳞癌的发生是由不同的分子机制和途径介导的。STAT3及其下游基因可作为小鼠和人肺腺癌和COPD诊断及预后的生物标志物。
Smoking causes lung cancer and chronic obstructive pulmonary disease (COPD) that impose severe health problem to humans. Both diseases are related to each other and can be induced by chronic inflammation in the lung. To identify the molecular mechanism for lung cancer formation, a CCSP-rtTA/(Teto)7Stat3C bitransgenic model was generated recently. In this model, persistent activation of the Stat3 signaling pathway induced pulmonary inflammation and adenocarcinoma formation in the lung. A group of Stat3 downstream genes were identified by Affymetrix GeneChip microarray analysis that can be used as biomarkers for lung cancer diagnosis and prognosis. To determine which human lung cancers are related to the Stat3 pathway, multiple Stat3 downstream genes were screened in human lung cancers (adenocarcinomas and squamous cell carcinomas) and lung tissue with COPD. In both cancer and COPD, the Stat3 gene was up-regulated. A panel of Stat3-up-regulated downstream genes in mice was up-regulated in human adenocarcinomas, but not in human squamous cell carcinomas. This panel of genes was also modestly up-regulated in lung tissue with COPD from patients with a history of smoking and not up-regulated in those without histories of smoking. Several Stat3-down-regulated downstream genes also showed differential expression patterns in carcinoma and COPD. These studies support a concept that Stat3 is a potent oncogenic molecule that plays a role in formation of lung adenocarcinomas in both mice and humans. The carcinogenesis of adenocarcinoma and squamous cell carcinoma is mediated by different molecular mechanisms and pathways in vivo. Stat3 and its downstream genes can serve as biomarkers for lung adenocarcinoma and COPD diagnosis and prognosis in mice and humans.
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DOI：
10.1016/j.bbrc.2007.11.069
发表时间：
2008-01-25
影响因子：
3.1
作者：
Liu, Zhilin;Ukomadu, Chinweike
通讯作者：
Ukomadu, Chinweike
影响因子：
11.2
作者：
Li, Yuan;Du, Hong;Yan, Cong
通讯作者：
Yan, Cong
DOI：
10.1016/j.bbrc.2006.09.018
发表时间：
2006-11-10
影响因子：
3.1
作者：
Rijken, D. C.;Dirkx, S. P. G.;Leebeek, F. W. G.
通讯作者：
Leebeek, F. W. G.
影响因子：
--
作者：
Yang, L;Lian, XM;Yan, C
通讯作者：
Yan, C
影响因子：
15.9
作者：
Gao, Sizhi Paul;Mark, Kevin G.;Bromberg, Jacqueline F.
通讯作者：
Bromberg, Jacqueline F.