| Autor: |
Reddy EM; National Centre for Cell Science, NCCS Complex, University of Pune Campus, Pune, Maharashtra, India., Chettiar ST, Kaur N, Ganeshkumar R, Shepal V, Shanbhag NC, Shiras A |
| Jazyk: |
angličtina |
| Zdroj: |
Cancer gene therapy [Cancer Gene Ther] 2011 Mar; Vol. 18 (3), pp. 206-18. Date of Electronic Publication: 2010 Nov 26. |
| DOI: |
10.1038/cgt.2010.71 |
| Abstrakt: |
We have previously reported the presence of Dlxin-1, a member of the melanoma antigen gene (MAGE) family, in the brain and showed its function as a cell cycle arrest protein, suggesting that Dlxin-1 may have anti-proliferative functions in rapidly growing tumors. Using the cancer stem cell hypothesis, which attributes the initiation and progression of brain tumors to the cancer-initiating stem cells, we have investigated the role of Dlxin-1 in the glioma stem cells propagated by us as a cell culture system comprising of HNGC-2 cells. Our studies provide evidence about the role of Dlxin-1 as an anti-tumorigenic protein in the highly chemo-resistant glioma stem cells. Next, we show that these anti-proliferative effects are manifested by Dlxin-1 through down regulation of the activities of MMP-2 and MMP-9, and through interaction of Dlxin-1 with its target protein P311 that is involved in glioma cell invasion. In summary, we establish the roles for Dlxin-1, one as an anti-tumorigenic and anti-invasive protein in high-grade gliomas and the other as an inducer of differentiation of glioma stem cells. These two attributes, in conjunction, result in conversion of the drug-resistant brain tumor stem cells to the tumor-attenuated cells that may now be more amenable to effective therapeutic targeting. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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