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Investigation of genes induced at the invasive front of lung adenocarcinomas

肺腺癌侵袭前沿诱导基因的研究

基本信息

批准号：
17590294
负责人：
NIKI Toshiro
金额：
$ 2.37万
依托单位：
Jichi Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590294/
关键词：
cancer cell and tissue signal transduction pathology

项目摘要

We constructed tissue microarray (TMA) that consisted of 5 cases of bronchiolo-alveolar carcinoma (BAC), 23 cases of mixed type adenocarcinoma with BAC component, and 20 cases of pure adenocarcinomas. Using this TMA, we investigated the expressions of (A) cell cycle regulators (p16, p21, p27, cyclin D1, and cyclin E), (B) tumor suppressors (p53, E-cadherin, PTEN, TSLC1, Smad3, and Smad4), and the results were compared between BAC, mixed adenocarcinoma, and pure adenocarcinomas. We found that (1) expressions of p16, p27, PTEN, E-cadherin, and TSLC1 were significantly decreased in pure adenocarcinomas compared to the other two groups, (2) expression of cyclin D1 was more frequently elevated in BAC and mixed adenocarcinomas than in pure adenocarcinomas, and (3) expression of Smad4 was maintained in BAC, but decreased in mixed and pure adenocarcinoms.We microdissected cancer cells from peripheral and central areas of mixed adenocarcinomas (n=7 and 5, respectively), and performed comprehensive gene expression analysis. Normal lung tissues (n=3) were also analyzed for comparison. Gene enrichment analysis demonstrated that gene sets induced by epithelial-mesenchymal transition (EMT) and hypoxia were overexpressed in the central vs. peripheral areas of mixed adenocarcinomas.To investigate the influence of hypoxia on cellular properties of cancer cells, we subjected lung adenocarcinoma cell line A549 to hypoxia, and gene expression profiles were analyzed by oligonuleotide arrays. The results showed that among the genes induced by hypoxia were those related to cell cycle, DNA repair, extracellular matrix synthesis, and angiogenesis. We also noted upregulation of EGFR and CXCR4, which may explain the motile phenotype that was induced by hypoxia. In fact, inhibition of EGFR completely abrogated the increase of motility caused by hypoxic treatment.

我们构建了5例细支气管肺泡癌（BAC）、23例BAC混合型腺癌和20例单纯腺癌的组织芯片（TMA）。使用该TMA，我们研究了（A）细胞周期调节因子（p16、p21、p27、cyclin D1和cyclin E），（B）肿瘤抑制因子（p53、E-cadherin、PTEN、TSLC 1、Smad 3和Smad 4）的表达，并将结果在BAC、混合腺癌和纯腺癌之间进行了比较。我们发现（1）p16、p27、PTEN、E-cadherin和TSLC 1在纯腺癌中的表达与其他两组相比显著降低，（2）cyclin D1在BAC和混合腺癌中的表达比纯腺癌更频繁地升高，（3）Smad 4在BAC中的表达维持不变，在混合型和单纯型腺癌中，我们显微解剖了来自混合型腺癌的外周和中央区域的癌细胞（分别为n=7和5），并进行了全面的基因表达分析。还分析了正常肺组织（n=3）进行比较。基因富集分析表明，由上皮间质转化（EMT）和低氧诱导的基因组在混合腺癌的中心区和周边区过度表达，为了研究低氧对癌细胞特性的影响，我们将肺腺癌细胞系A549置于低氧环境中，用寡核苷酸芯片分析基因表达谱。结果表明，在低氧诱导的基因中，有与细胞周期、DNA修复、细胞外基质合成和血管生成相关的基因。我们还注意到EGFR和CXCR 4的上调，这可能解释了缺氧诱导的运动表型。事实上，EGFR的抑制完全消除了由低氧处理引起的运动性增加。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Hypoxia increases the motility of lung adenocarcinoma cells A549 via activation of the epidermal growth factor receptor pathway.

缺氧通过激活表皮生长因子受体途径增加肺腺癌细胞 A549 的运动性。

DOI：
发表时间：
2007
期刊：
Cancer Sci (In press)
影响因子：
0
作者：
Wang T;et al.
通讯作者：
et al.

Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas

DOI：
10.1158/1078-0432.ccr-04-1238
发表时间：
2005-03-01
期刊：
CLINICAL CANCER RESEARCH
影响因子：
11.5
作者：
Fukumoto, S;Yamauchi, N;Aburatani, H
通讯作者：
Aburatani, H

Differential expression of S100A2 and S100A4 in lung adenocarcinomas : clinicopathologic significance, relationship to p53, and identification of their target genes.

S100A2 和 S100A4 在肺腺癌中的差异表达：临床病理意义、与 p53 的关系及其靶基因的鉴定。

DOI：
发表时间：
2005
期刊：
Cancer Sci 96
影响因子：
0
作者：
Tanaka-Fujita;R.;Soeno;Y;Satoh;H.;Nakamura;Y. and Mori;S.;Randa Amin;Matsubara D.et al.
通讯作者：
Matsubara D.et al.

Cytoplasmic localization of p63 is associated with poor patient survival in lung adenocarchinoma.

p63 的细胞质定位与肺腺癌患者的较差生存率相关。