High expression of a novel splicing variant of VEGF, L-VEGF144 in glioblastoma multiforme is associated with a poorer prognosis in bevacizumab treatment
| Autor: | Chiung-Chyi Shen, Tsuo-Fei Mao, Yea-Jiuan Liang, Jun-Peng Chen, Wen-Yu Cheng, Bai-Shuan Liu, Ming-Tsang Chiao |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Vascular Endothelial Growth Factor A 0301 basic medicine Cancer Research Bevacizumab Nucleolus Biology 03 medical and health sciences Exon chemistry.chemical_compound Antineoplastic Agents Immunological 0302 clinical medicine Temozolomide medicine Humans Antineoplastic Agents Alkylating Cell Line Transformed Cell Proliferation Brain Neoplasms Exons Transfection Middle Aged Prognosis In vitro Gene Expression Regulation Neoplastic Vascular endothelial growth factor 030104 developmental biology Neurology Oncology chemistry 030220 oncology & carcinogenesis Mutation RNA splicing Cancer research Female Neurology (clinical) Glioblastoma Cell Nucleolus Follow-Up Studies medicine.drug |
| Zdroj: | Journal of Neuro-Oncology. 140:37-47 |
| ISSN: | 1573-7373 0167-594X |
| DOI: | 10.1007/s11060-018-2928-z |
| Popis: | A previous study confirmed that a novel splicing variant of large vascular endothelial growth factor (L-VEGF) termed L-VEGF144, a nucleolus protein, is found in glioblastoma cells and specimens, but the actual biological function and clinical significance of L-VEGF144 remain unclear. In this study, we analyzed the expression of L-VEGF144 in 68 glioblastoma multiforme specimens using reverse transcriptase-polymerase chain reaction analysis. The results showed that the high expression of L-VEGF144 was associated with a poor prognosis in the bevacizumab plus concurrent chemoradiotherapy with temozolomide treatment. In addition, we constructed a series truncated and mutant form of L-VEGF144 to confirm that exon 6a of L-VEGF144 is able to engage in the nuclear importation and found that 8 lysines within exon 6a play a critical role in the nucleolus aggregation of L-VEGF144. Also, the transfection of the L-VEGF144 increased the number of nucleoli. Furthermore, the recombinant protein Flag-L-VEGF144 and commercial VEGF protein have similar growth stimulatory activities in terms of inducing glioblastoma cell proliferation in vitro. Taken together, these results indicated that the expression of L-VEGF144 could potentially serve as an independent indicator of poor prognosis in bevacizumab treatment. |
| Databáze: | OpenAIRE |
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