Abstract |
Neuropilin-1 (NRP-1) is a non- tyrosine kinase receptor for vascular endothelial growth factor ( VEGF) that was recently found to play a role in tumor functions. Previous studies demonstrated that NRP-1 was overexpressed in a number of human tumors, including glioblastoma (GBM). However, the role of NRP-1 in glioma progression has yet to be adequately elucidated. Thus, we examined the expression of NRP-1 in human glioma cell lines using Western blotting, and cell cycle distribution and proliferation by transfection of the U373 cell line with NRP-1 short interference RNA ( siRNA). Results showed NRP-1 siRNA to significantly reduce NRP-1 gene expression, decrease in vitro cell proliferation and induce cell apoptosis in cultured glioma cells, along with the accumulation of cells in the G1 phase and a decrease in cells in the S phase. Our results further revealed that NRP-1 knockdown decreased the expression levels of Bcl-2 family proteins and deactivated extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK)/ mitogen-activated protein kinase (MAPK) signaling pathways, closely associated with cancer progression. Thus, our results provide a molecular mechanism for the effect of NRP-1 in tumors, rendering NRP-1 an attractive candidate as a therapeutic target in certain types of cancer, such as GBM.
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Authors | Xiangyun Li, Ting Tang, Xiaozhe Lu, Houguang Zhou, Yanyan Huang |
Journal | Molecular medicine reports
(Mol Med Rep)
2011 Nov-Dec
Vol. 4
Issue 6
Pg. 1261-6
ISSN: 1791-3004 [Electronic] Greece |
PMID | 21842123
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Proto-Oncogene Proteins c-bcl-2
- RNA, Small Interfering
- Neuropilin-1
- Extracellular Signal-Regulated MAP Kinases
- JNK Mitogen-Activated Protein Kinases
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Topics |
- Apoptosis
(drug effects)
- Brain Neoplasms
(metabolism, pathology)
- Cell Line, Tumor
- Cell Proliferation
- Extracellular Signal-Regulated MAP Kinases
(metabolism)
- G1 Phase Cell Cycle Checkpoints
(drug effects)
- Glioma
(metabolism, pathology)
- Humans
- JNK Mitogen-Activated Protein Kinases
(metabolism)
- MAP Kinase Signaling System
(drug effects)
- Neuropilin-1
(antagonists & inhibitors, genetics, metabolism)
- Proto-Oncogene Proteins c-bcl-2
(metabolism)
- RNA Interference
- RNA, Small Interfering
(metabolism, pharmacology)
- S Phase Cell Cycle Checkpoints
(drug effects)
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