Cancer Lett 2011 Dec;312 (1): 18-23. [IF:4.864]
Exploration of target genes of HOXA13 in esophageal squamous cell carcinoma cell line.
Shen LY , Chen KN .
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing 100036, PR China.
北京大学恶性肿瘤发病机制及转化研究教育部重点实验室，北京肿瘤医院研究所胸外科，北京大学肿瘤学院
Abstract
Homeobox genes encode transcriptional factors which regulate cell proliferation and differentiation and have been found to be deregulated in many tumors. Previously, we found that the median survival time of patients with ESCC (Esophageal squamous cell carcinoma) expressing HOXA13 was significantly shorter than those with HOXA13-negative ESCC and we also demonstrated that knockdown of HOXA13 blocked cell proliferation in vitro and in vivo. In this study, we examined the protein expression changes after HOXA13 knockdown by 2-dimentional electrophoresis. Forty-five spots were significantly different, among which 24 were down-regulated and 21 were up-regulated after HOXA13 knockdown. The proteins from 14 gel-spots were further characterized by MALDI-TOF MS, among which, AnnexinA2, MnSOD and ERAB, are validated by Western Blot analysis. Transcriptional target analysis revealed that HOXA13 regulated several cell signaling pathways that are critically involved in cell proliferation, survival and migration. These results provide an additional support to a hypothesis that HOXA13 might participate in the carcinogenesis of ESCC.
摘要：
在许多类型的肿瘤中，编码调节细胞增殖分化的转录因子的同源基因都有下调。之前我们的研究发现，HOXA13阳性的食管鳞癌（ESCC）的患者，其中位生存期都比HOXA13阴性患者要短得多。我们在体内和体外实验中也都证实，敲除HOXA13能够阻断细胞增殖。在本研究中，我们用双向电泳技术检测敲除HOXA13基因后的蛋白表达变化。我们发现在敲除HOXA13基因后，55个凝胶点发生了显著的变化，其中24个表达下调，另外21个上调。我们用MALDI-TOF MS技术进一步鉴定了14个凝胶点上的蛋白，发现其中包括AnnexinA2, MnSOD 和 ERAB，并用Western Blot进行了确认。转录目标分析显示HOX13调节那些和细胞增殖，存活和转移密切相关的细胞信号通路。这些实验结果为HOXA13基因参与ESCC发生发展这一假说提供了进一步的证据。
