Upregulation of SOX9 in Lung Adenocarcinoma and Its Involvement in the Regulation of Cell Growth and Tumorigenicity
Upregulation of SOX9 in Lung Adenocarcinoma and Its Involvement in the Regulation of Cell Growth and Tumorigenicity
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DOI：
10.1158/1078-0432.ccr-10-0138
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发表时间：
2010-09-01
影响因子：
11.5
通讯作者：
Chang, I-Shou
中科院分区：
文献类型：
--
作者：
Jiang, Shih Sheng;Fang, Wen-Tsen;Chang, I-Shou
目的：SOX 9是发育所需的重要转录因子，并与几种类型的癌症有关。然而，迄今为止，SOX 9从未与肺癌有关。在这里，我们发现SOX 9表达在肺腺癌中上调，并显示它如何与癌细胞生长相关。实验设计：对包含490个临床样本的5个微阵列数据集进行数据挖掘，对57个独立样本进行定量逆转录PCR验证试验，采用免疫组织化学方法检测170例肺组织中SOX 9 mRNA和蛋白的表达。结果：SOX 9 mRNA和蛋白在肺腺癌组织中呈高表达，在肺腺癌组织中呈高表达，在肺腺癌组织中呈高表达。在肺腺癌细胞系中敲低SOX 9导致粘附性和锚定非依赖性生长的显著减少，这与p21（CDKN 1A）的上调和CDK 4的下调一致。与肺腺癌中较高的SOX 9表达水平一致，肿瘤中p21 mRNA水平显著低于正常组织，而CDK 4则相反，支持SOX 9分别负性和正性调节p21和CDK 4的观点。最后，而SOX 9敲低细胞表现出显着衰减的致瘤性在小鼠中，SOX 9转染一贯表现出显着更强的tumorigenicity.Conclusions：我们的数据表明，SOX 9是一个新的标志肺腺癌，其中SOX 9可能有助于获得的肿瘤生长潜力，可能通过影响细胞周期调节因子p21和CDK 4的表达。临床癌症研究; 16（17）; 4363-73。(C)2010年AACR。
Purpose: SOX9 is an important transcription factor required for development and has been implicated in several types of cancer. However, SOX9 has never been linked to lung cancer to date. Here, we show that SOX9 expression is upregulated in lung adenocarcinoma and show how it is associated with cancer cell growth.Experimental Design: Data mining with five microarray data sets containing 490 clinical samples, quantitative reverse transcription-PCR validation assay in 57 independent samples, and immunohistochemistry assay with tissue microarrays containing 170 lung tissue cores were used to profile SOX9 mRNA and protein expression. Short interference RNA suppression of SOX9 in cell lines was used to scrutinize functional role(s) of SOX9 and associated molecular mechanisms.Results: SOX9 mRNA and protein were consistently overexpressed in the majority of lung adenocarcinoma. Knockdown of SOX9 in lung adenocarcinoma cell lines resulted in marked decrease of adhesive and anchorage-independent growth in concordance with the upregulation of p21 (CDKN1A) and down-regulation of CDK4. In agreement with higher SOX9 expression level in lung adenocarcinoma, the p21 mRNA level was significantly lower in tumors than that in normal tissues, whereas the opposite was true for CDK4, supporting the notion that SOX9 negatively and positively regulated p21 and CDK4, respectively. Finally, whereas SOX9-knockdown cells showed significantly attenuated tumorigenicity in mice, SOX9 transfectants consistently showed markedly stronger tumorigenicity.Conclusions: Our data suggest that SOX9 is a new hallmark of lung adenocarcinoma, in which SOX9 might contribute to gain of tumor growth potential, possibly acting through affecting the expression of cell cycle regulators p21 and CDK4. Clin Cancer Res; 16(17); 4363-73. (C) 2010 AACR.