Cold shock domain protein A represses angiogenesis and lymphangiogenesis via inhibition of serum response element
| Autor: | Yoshimi Saito, Hiroki Hayashi, Yoichi Takami, Hironori Nakagami, Katsuto Tamai, Tadahiro Sasajima, Ryuichi Morishita, Yasufumi Kaneda, Masayuki Kurooka, Nobuyoshi Azuma, Tomoyuki Nishikawa, Yasushi Kikuchi |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
Cancer Research Angiogenesis Response element Angiogenesis Inhibitors Biology Response Elements Carcinoma Lewis Lung Mice chemistry.chemical_compound Dogs Chlorocebus aethiops Genetics Animals Humans Lymphangiogenesis Hypoxia Promoter Regions Genetic Molecular Biology Transcription factor Aorta Cells Cultured Cell Proliferation Gene Library Neovascularization Pathologic Genes fos Cold-shock domain Serum Response Element DNA-Binding Proteins Mice Inbred C57BL Endothelial stem cell chemistry COS Cells Cancer research Cattle Endothelium Vascular Endothelium Lymphatic Growth inhibition Transcription Factors |
| Zdroj: | Oncogene. 27:1821-1833 |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | Dual-targeted therapy for antiangiogenesis and antilymphangiogenesis represents a potentially effective strategy for the treatment of various malignancies. Therefore, the goal of the present study was to identify genes that encode inhibitors of both angiogenesis and lymphangiogenesis. Using a cDNA library obtained from Lewis lung carcinoma (LL/2), a candidate gene was identified by the evaluation of growth inhibition in aortic and lymphatic endothelial cells (EC) as that coding for the mouse cold shock domain protein A (mCSDA). Overexpression of mCSDA significantly repressed cell proliferation and c-fos promoter activity in aortic, venous and lymphatic ECs. CSDA is a DNA-binding protein that binds to the hypoxia response element (HRE). Furthermore, of importance, we revealed that CSDA could directly bind to the serum response element (SRE) sequence, resulting in the inhibition of SRE activity, which may lead to growth inhibition in ECs. In an LL/2-inoculated mouse model, tumor growth was significantly repressed in an mCSDA-injected group. Histopathological analysis revealed that expression of blood and lymphatic EC markers was significantly decreased in mCSDA-injected groups. In conclusion, these data suggest that expression of CSDA can repress angiogenesis and lymphangiogenesis via direct binding to SRE in addition to HRE. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|