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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Paul-Samojedny, Monika Pudelko, Adam Suchanek-Raif, Renata Kowalczyk, Malgorzata Fila-Danilow, Anna Borkowska, Paulina Kowalski, Jan |
| Description | Author Affiliation: Paul-Samojedny M ( Department of Medical Genetics, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Jednosci 8 Street, 41-200, Katowice, Sosnowiec, Poland, mpaul@sum.edu.pl.) |
| Abstract | Glioblastoma multiforme (GBM) is the most common primary brain malignancy, having a very poor prognosis and is characterized by extensive brain invasion as well as resistance to the therapy. The phosphoinositide 3-kinase (PI3K)/Akt/PTEN signaling pathway is deregulated in GBM. Besides, florid vascularization and aberrantly elevated vascular endothelial growth factor (VEGF) occur very often. The present study was designed to examine the inhibitory effect of AKT3, PI3KCA, and VEGFR2 small interfering RNAs (siRNAs) on GBM cell invasiveness. T98G cells were transfected with AKT3, PI3KCA, and/or VEGFR2 siRNAs. VEGFR2 protein-positive cells were identified by flow cytometry using specific monoclonal anti-VEGFR2 antibodies. Alterations in messenger RNA (mRNA) expression of VEGF, VEGFR2, matrix metalloproteinases (MMPs) (MMP-2, MMP-9, MMP-13, MMP-14), tissue inhibitors of metalloproteinases (TIMPs) (TIMP-1, TIMP-3), c-Fos, c-Jun, hypoxia-inducible factor-1 (HIF-1 ), ObRa, and cathepsin D genes were analyzed by qRT-PCR. Cells treated with specific siRNA were also analyzed for invasion using the Matrigel invasion assay. We have found significantly lower mRNA levels of MMPs, cathepsin D, VEGF, VEGFR2, HIF-1 , and c-Fos/c-Jun ratio, as well as significantly higher mRNA level of TIMPs in AKT3 and PI3KCA siRNA transfected cells compared to untransfected cells, while significantly lower mRNA levels of MMPs (MMP-2, MMP-9, MMP-14) and TIMP-1, as well as significantly higher mRNA level of TIMP-3, were shown only in cells transfected with VEGFR2 siRNA. The positive correlation between MMP-13 and ObRa mRNA copy number has been found. Summarizing, transfection of T98G cells with AKT3, PI3KCA, or VEGFR2 siRNAs leads to a significant reduction in cell invasiveness. The siRNA-induced AKT3, PI3KCA, and VEGFR2 mRNA knockdown may offer a novel therapeutic strategy to reduce the invasiveness of GBM cells. |
| File Format | HTM / HTML |
| ISSN | 10104283 |
| Issue Number | 5 |
| Volume Number | 36 |
| e-ISSN | 14230380 |
| Journal | Tumor Biology |
| Language | English |
| Publisher | Springer |
| Publisher Date | 2015-05-01 |
| Publisher Place | Netherlands |
| Access Restriction | Subscribed |
| Subject Keyword | Discipline Medicine__semicolon__oncology Brain Neoplasms Enzymology Glioblastoma Metabolism Nuclear Proteins Genetics Proto-oncogene Proteins C-akt Transcription Factors Vascular Endothelial Growth Factor Receptor-2 Pathology Cell Line, Tumor Cell Movement Gene Knockdown Techniques Humans Matrix Metalloproteinases, Secreted Rna Interference Rna, Messenger Rna, Small Interfering Tissue Inhibitor Of Metalloproteinase-3 Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Cancer Research |
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