IGFBP3, a transcriptional target of homeobox D10, is correlated with the prognosis of gastric cancer

• Published in: PloS one 2013-12, Vol.8 (12), p.e81423-e81423
• Main Authors: Xue, Meng, Fang, Yanfei, Sun, Guoming, Zhuo, Wei, Zhong, Jing, Qian, Cuijuan, Wang, Lan, Wang, Liangjing, Si, Jianmin, Chen, Shujie
• Format: Article
• Language: English
• Subjects: Angiogenesis; Binding sites; Breast cancer; Cancer; Cancer metastasis; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell survival; Chromatin; Deoxyribonucleic acid; DNA; DNA methylation; Ectopic expression; Endometrial cancer; Gastric cancer; Gastroenterology; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Genes; Genetic aspects; Homeobox; Homeodomain Proteins - genetics; Homeodomain Proteins - physiology; Humans; Immunohistochemistry; Immunoprecipitation; Insulin; Insulin-Like Growth Factor Binding Protein 3 - genetics; Insulin-like growth factor-binding protein 3; Insulin-like growth factors; Invasiveness; Luciferase; Lymph; Lymph nodes; Matrix Metalloproteinase 14 - genetics; Matrix Metalloproteinase 14 - metabolism; Medical prognosis; Metastases; Metastasis; Neoplasm Invasiveness - genetics; Patients; Prognosis; Promoter Regions, Genetic; Prostate; Protein binding; Proteins; Receptors, Urokinase Plasminogen Activator - genetics; Receptors, Urokinase Plasminogen Activator - metabolism; Stomach cancer; Stomach Neoplasms - diagnosis; Stomach Neoplasms - genetics; Studies; Survival; Survival Analysis; Tissues; Transcription; Transcription (Genetics); Transcription Factors - genetics; Transcription Factors - physiology; Up-Regulation; Urokinase-Type Plasminogen Activator - genetics; Urokinase-Type Plasminogen Activator - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0081423

Homeobox D10 (HoxD10) plays important roles in the differentiation of embryonic cells and progression of breast cancer. Our previous report revealed that insulin-like growth factor binding protein-3 (IGFBP3) was regulated by HoxD10 in gastric cancer cells; however, the functional roles and underlying mechanisms of IGFBP3 in gastric cancer remain unclear. Here, we found that the expression of IGFBP3 were upregulated after ectopic expression of HoxD10 in gastric cancer cells. Chromatin immunoprecipitation assay showed that HoxD10 bound to three potential regions of IGFBP3 promoter. Exogenous HoxD10 significantly enhanced the activity of luciferase reporter containing these binding regions in gastric cancer cells. Further data showed that all of these binding sites had Hox binding element "TTAT". Immunohistochemical staining results revealed that IGFBP3 expression was significantly downregulated in 86 gastric adenocarcinomas tissues relative to their adjacent non-cancerous tissues (p