Profiling of transcripts and proteins modulated by K-ras oncogene in the Rung tissues of K-ras transgenic mice by omics approaches
Profiling of transcripts and proteins modulated by K-ras oncogene in the Rung tissues of K-ras transgenic mice by omics approaches
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DOI：
10.3892/ijo_00000138
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发表时间：
2009-01-01
影响因子：
5.2
通讯作者：
Yoon, Do-Young
中科院分区：
文献类型：
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作者：
Lee, Sojung;Kang, Jungwoo;Yoon, Do-Young
突变的 K-ras 基因与大约 30% 的人类癌症有关。为了在K-ras转基因小鼠的肺组织中寻找K-ras癌基因诱导的调节剂，我们进行了微阵列和蛋白质组学（LC/ESI-MS/MS）分析。与癌症发展（Wnt信号通路）和炎症（趋化因子/细胞因子信号通路、Toll受体信号通路）相关的基因（RAB27b RAS家族、IL-1RA、IL-33、趋化因子配体6、上皮调节蛋白、EGF样结构域和组织蛋白酶）上调，而基因（肌钙蛋白、原调节蛋白2、内皮脂肪酶、 K-ras癌基因下调与肿瘤抑制相关的FGFR4、整合素α8和腺苷酸环化酶8），如p53通路、TGF-β信号通路和钙粘蛋白信号通路。蛋白质组学方法显示，K-ras小鼠肺腺瘤中上调的蛋白质分为以下几类：与代谢/分解代谢相关的蛋白质（K-ras基因从7%增加到22%）、与翻译/转录和核苷酸相关的蛋白质（从4%增加到6%）、与信号转导相关的蛋白质（从3%增加到5%）、与磷酸化相关的蛋白质（从1%增加到5%）。 2%）。 ATP合酶、Ras癌基因家族、细胞色素c氧化酶、黄素蛋白、TEF 1、脂肪蛋白A-1 BP、谷胱甘肽氧化酶、脂肪酸BP 4、心肌黄酶1、MAPK4和转胶蛋白被K-ras癌基因上调。然而，整合素 α 1、Ras 相互作用蛋白 (Rain)、内皮素转换酶 1d 和剪接因子 3b 下调。这些研究表明。 K-ras 上调与癌症发展和炎症相关的基因，而下调与肿瘤抑制相关的基因，从而导致肿瘤生长。假定的生物标志物，例如细胞周期相关基因 (Cdc37)、癌细胞粘附（Glycam 1、整合素 α 8、整合素 α X 和 Clec4n）、信号转导（Tlr2、IL-33 和 Ccbp2）、迁移（Ccr1、Cc16 和心肌黄酶 1 (Cyb5r3) 和癌症发展（上皮调节蛋白）可用于 诊断和预后标志物，一些靶分子可用于预防癌症。
The mutated K-ras gene is involved in similar to 30% of human cancers. In order to search for K-ras oncogene-induced modulators in lung tissues of K-ras transgenic mice, we performed microarray and proteomics (LC/ESI-MS/MS),analysis. Genes (RAB27b RAS family, IL-1RA, IL-33, chemokine ligand 6, epiregulin, EGF-like domain and cathepsin) related to cancer development (Wnt signaling pathway) and inflammation (chemokine/cytokine signaling pathway, Toll receptor signaling) were up-regulated while genes (troponin, tropomodulin 2, endothelial lipase, FGFR4, integrin alpha 8 and adenylate cyclase 8) related to the tumor suppression Such as p53 pathway, TGF-beta signaling pathway and cadherin signaling pathway were down-regulated by K-ras oncogene. Proteomics approach revealed that upregulated proteins in lung adenomas of K-ras mice were classified as follows: proteins related to the metabolism/catabolism (increased from 7 to 22% by K-ras gene), proteins related to translation/transcription and nucleotide (from 4 to 6%), proteins related to signal transduction (from 3 to 5%), proteins related to phosphorylation (from 1 to 2%). ATP synthase, Ras oncogene family, cytochrome c oxidase, flavoprotein, TEF 1, adipoprotein A-1 BP, glutathione oxidase, fatty acid BP 4, diaphorase 1, MAPK4 and transgelin were up-regulated by K-ras oncogene. However, integrin alpha 1, Ras-interacting protein (Rain), endothelin-converting enzyme-1d and splicing factor 3b were down-regulated. These studies suggest that. genes related to cancer development and inflammation were up-regulated while genes related to the tumor suppression were down-regulated by K-ras, resulting in the tumor growth. Putative biomarkers such as cell cycle \related genes (Cdc37), cancer cell adhesion (Glycam 1, integrin alpha 8, integrin alpha X and Clec4n), signal transduction (Tlr2, IL-33, and Ccbp2), migration (Ccr1, Cc16, and diaphorase 1 (Cyb5r3) and cancer development (epiregulin) can be useful for diagnosis and as prognosis markers and some of the target molecules can be applied for prevention of cancer.