Academic Journal
Transcriptional Regulation of Vascular Endothelial Growth Factor C by Oxidative and Thermal Stress Is Mediated by Lens Epithelium-Derived Growth Factor/p75
| Title: | Transcriptional Regulation of Vascular Endothelial Growth Factor C by Oxidative and Thermal Stress Is Mediated by Lens Epithelium-Derived Growth Factor/p75 |
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| Authors: | Batya Cohen, Yoseph Addadi, Stav Sapoznik, Gila Meir, Vyacheslav Kalchenko, Alon Harmelin, Shifra Ben-Dor, Michal Neeman |
| Source: | Neoplasia: An International Journal for Oncology Research, Vol 11, Iss 9, Pp 921-933 (2009) |
| Publisher Information: | Elsevier, 2009. |
| Publication Year: | 2009 |
| Collection: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: | Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: | Vascular endothelial growth factor C (VEGF-C) plays a critical role in tumor lymphangiogenesis and lymph node metastasis. We report here that VEGF-C expression is regulated by microenvironmental stress including hyperthermia and oxidative stress. Furthermore, we show that this stress response is mediated by transcriptional activation mediated by lens epithelium-derived growth factor (LEDGF/p75). Ectopic expression of LEDGF/p75 in C6 rat glioma and in H1299 human non-small cell lung carcinoma induced VEGF-C expression in vitro, whereas in subcutaneous mouse tumor xenografts, LEDGF/p75 stimulated VEGF-C expression and augmented angiogenesis and lymphangiogenesis. Conversely, overexpression of a LEDGF/p75 native antisense or LEDGF/p75-targeted short interfering RNA downmodulated VEGF-C expression. LEDGF seemed to conferred this activity on binding to a conserved stress response element (STRE) located in the VEGF-C gene because mutating the STRE was sufficient for the suppression of basal and stress-induced activations of the VEGF-C promoter. Thus, the study reported here identified a role for LEDGF/p75 in stress-regulated transcriptional control of VEGF-C expression. These results provide a possible link for LEDGF/p75 in tumor lymphangiogenesis and cancer metastasis. Hence, our data suggest the LEDGF-VEGF-C axis as a putative biomarker for the detection of stress-induced lymphangiogenesis and LEDGF as a potential target for antimetastatic therapy. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1476-5586 1522-8002 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S1476558609800456; https://doaj.org/toc/1476-5586; https://doaj.org/toc/1522-8002 |
| DOI: | 10.1593/neo.09636 |
| Access URL: | https://doaj.org/article/84c9f090dd42486aa52becd0e195f7a9 |
| Accession Number: | edsdoj.84c9f090dd42486aa52becd0e195f7a9 |
| Database: | Directory of Open Access Journals |
| ISSN: | 14765586 15228002 |
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| DOI: | 10.1593/neo.09636 |
| Published in: | Neoplasia: An International Journal for Oncology Research |
| Language: | English |