Meta-analysis of oncogenic protein kinase Ciota signaling in lung adenocarcinoma.
Meta-analysis of oncogenic protein kinase Ciota signaling in lung adenocarcinoma.
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DOI：
10.1158/1078-0432.ccr-08-2459
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发表时间：
2009-03-01
期刊：
影响因子：
--
通讯作者：
Fields AP
中科院分区：
文献类型：
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作者：
Erdogan E;Klee EW;Thompson EA;Fields AP
非典型蛋白激酶C1（PKC 1）是非小细胞肺癌（NSCLC）中的癌基因。在这里，我们确定了肺腺癌（LAC）（NSCLC的最主要形式）中PKCι的四个功能性基因靶标。询问三个独立的公共领域基因表达数据集以鉴定与原发性LAC肿瘤中的PKCι协同表达的基因。在一组独立的原发性LAC肿瘤中通过QPCR验证结果。使用RNAi介导的PKC1和靶基因的敲低来确定所鉴定的基因的表达是否受PKC1调节，以及这些靶基因是否在LAC细胞的锚定非依赖性生长和侵袭中起作用。荟萃分析确定了7个基因的表达与原发性LAC中的PKCι相关。随后的QPCR分析证实了在一组独立的LAC样品中四种基因（COPB 2、ELF 3、RFC 4和PLS 1）的协同过表达。RNAi介导的敲除表明，PKCι调节LAC细胞中所有四个基因的表达，并且四个PKCι靶基因在LAC细胞的非贴壁依赖性生长和侵袭中起重要作用。来自肺鳞状细胞癌、乳腺癌、结肠癌、前列腺癌和胰腺癌以及胶质母细胞瘤的基因表达数据集的荟萃分析揭示，PKC 1靶基因的子集，特别是COPB 2和RFC 4，与许多肿瘤类型中的PKC 1表达相关。公开基因表达数据的荟萃分析可用于鉴定致癌PKC 1信号传导的新基因靶标。我们的数据表明，共同的和细胞类型特异性的信号传导机制都有助于PKC i依赖性转化。
Atypical protein kinase Cι (PKCι) is an oncogene in non – small cell lung cancer (NSCLC). Here, we identify four functional gene targets of PKCι in lung adenocarcinoma (LAC), the most prominent form of NSCLC. Three independent public domain gene expression data sets were interrogated to identify genes coordinately expressed with PKCι in primary LAC tumors. Results were validated by QPCR in an independent set of primary LAC tumors. RNAi-mediated knockdown of PKCι and the target genes was used to determine whether expression of the identified genes was regulated by PKCι, and whether these target genes play a role in anchorage-independent growth and invasion of LAC cells. Meta-analysis identified seven genes whose expression correlated with PKCι in primary LAC. Subsequent QPCR analysis confirmed coordinate overexpression of four genes (COPB2, ELF3, RFC4, and PLS1) in an independent set of LAC samples. RNAi-mediated knockdown showed that PKCι regulates expression of all four genes in LAC cells, and that the four PKCι target genes play an important role in the anchorage-independent growth and invasion of LAC cells. Meta-analysis of gene expression data sets from lung squamous cell, breast, colon, prostate, and pancreas carcinomas, as well as glioblastoma, revealed that a subset of PKCι target genes, particularly COPB2 and RFC4, correlate with PKCι expression in many tumor types. Meta-analysis of public gene expression data are useful in identifying novel gene targets of oncogenic PKCι signaling. Our data indicate that both common and cell type – specific signaling mechanisms contribute to PKCι-dependent transformation.