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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Zhang, Keqiang Hu, Shuya Wu, Jun Chen, Linling Lu, Jianming Wang, Xiaochen Liu, Xiyong Zhou, Bingsen Yen, Yun |
| Abstract | Background In addition to its essential role in ribonucleotide reduction, ribonucleotide reductase (RNR) small subunit, RRM2, has been known to play a critical role in determining tumor malignancy. Overexpression of RRM2 significantly enhances the invasive and metastatic potential of tumor. Angiogenesis is critical to tumor malignancy; it plays an essential role in tumor growth and metastasis. It is important to investigate whether the angiogenic potential of tumor is affected by RRM2. Results We examined the expression of antiangiogenic thrombospondin-1 (TSP-1) and proangiogenic vascular endothelial growth factor (VEGF) in two RRM2-overexpressing KB cells: KB-M2-D and KB-HURs. We found that TSP-1 was significantly decreased in both KB-M2-D and KB-HURs cells compared to the parental KB and mock transfected KB-V. Simultaneously, RRM2-overexpressing KB cells showed increased production of VEGF mRNA and protein. In contrast, attenuating RRM2 expression via siRNA resulted in a significant increased TSP-1 expression in both KB and LNCaP cells; while the expression of VEGF by the two cells was significantly decreased under both normoxia and hypoxia. In comparison with KB-V, overexpression of RRM2 had no significant effect on proliferation in vitro, but it dramatically accelerated in vivo subcutaneous growth of KB-M2-D. KB-M2-D possessed more angiogenic potential than KB-V, as shown in vitro by its increased chemotaxis for endothelial cells and in vivo by the generation of more vascularized tumor xenografts. Conclusion These findings suggest a positive role of RRM2 in tumor angiogenesis and growth through regulation of the expression of TSP-1 and VEGF. |
| Related Links | https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/1476-4598-8-11.pdf |
| Ending Page | 12 |
| Page Count | 12 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14764598 |
| DOI | 10.1186/1476-4598-8-11 |
| Journal | Molecular Cancer |
| Issue Number | 1 |
| Volume Number | 8 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2009-02-28 |
| Access Restriction | Open |
| Subject Keyword | Cancer Research Oncology Vascular Endothelial Growth Factor Human Umbilical Vein Endothelial Cell Vascular Endothelial Growth Factor Expression LNCaP Cell Vascular Endothelial Growth Factor mRNA |
| Content Type | Text |
| Resource Type | Article |
| Subject | Oncology Molecular Medicine Cancer Research |
| Journal Impact Factor | 27.7/2023 |
| 5-Year Journal Impact Factor | 31.3/2023 |
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