Document Detail


Effect of wild type PTEN gene on proliferation and invasion of multiple myeloma.
MedLine Citation:
PMID:  20582577     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We explored the effect of the wild type PTEN gene on the proliferation, apoptosis and invasive ability of multiple myeloma (MM) cells from MM patients and RPMI 8226 cells (a human myeloma cell line), and the effect of the PTEN/focal adhesion kinase (FAK)/MMP signaling pathway on the invasion activity of RPMI 8226 cells. The proliferation of RPMI 8226 cells and purified myeloma cells from MM patients were markedly inhibited after these cells were transfected with recombinant adenovirus-PTEN vectors containing green fluorescent protein (Ad-PTEN-GFP). Maximum growth inhibition of RPMI 8226 cells and purified myeloma cells from MM patients by AD-PTEN-GFP was 42.01 and 24.75%, respectively. After transfection with PTEN-siRNA, the proliferation of RPMI 8226 cells was increased significantly compared with NS-siRNA transfected controls. The maximal survival rate was 141.55 +/- 8.34% in PTEN-siRNA transfected RPMI 8226 cells. Apoptosis of RPMI 8226 cells or purified myeloma cells from MM patients in the Ad-PTEN-GFP group was increased significantly when compared with that in the Ad-GFP (adenovirus vectors only expressing green fluorescent protein) group (p < 0.01). The cell cycle of RPMI 8226 cells was arrested at the G2/M phase. Furthermore, the number of cells that migrated through the matrigel and filter from the upper chamber to the lower chamber in the transwell assay in the Ad-GFP group was significantly larger than that in the Ad-PTEN-GFP group (52.65 +/- 7.39 vs. 23.50 +/- 6.12, p < 0.01). In the PTEN-siRNA group, the cell number (79.50 +/- 11.89) was significantly larger than that in the NS-siRNA group (47.17 +/- 7.76, p < 0.01). When RPMI 8226 cells were transfected with Ad-PTEN-GFP or NS-siRNA, the expression level of PTEN mRNA was up-regulated, and the expression levels of FAK, MMP-2 and MMP-9 mRNA were down-regulated significantly compared with that of the Ad-GFP group and the PTEN-siRNA group (p < 0.01, p < 0.05). The protein levels of FAK and p-FAK, MMP-2 and MMP-9 in RPMI 8226 cells which were transfected with Ad-PTEN-GFP decreased significantly, but increased significantly in PTEN-siRNA transfected RPMI 8226 cells (p < 0.01, p<0.05). These results indicated that wild type PTEN, which inhibited FAK, MMP-2, and MMP-9, could suppress the proliferation and invasion ability of multiple myeloma cells. Modulating the expression of PTEN may be a potential strategy for the treatment of multiple myeloma.
Authors:
Suyun Wang; Zhiyong Cheng; Xiaoyang Yang; Kai Deng; Yan Cao; Hao Chen; Ling Pan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-26
Journal Detail:
Title:  International journal of hematology     Volume:  92     ISSN:  1865-3774     ISO Abbreviation:  Int. J. Hematol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-08-02     Completed Date:  2010-12-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9111627     Medline TA:  Int J Hematol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  83-94     Citation Subset:  IM    
Affiliation:
Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Gene Therapy / methods
Humans
Multiple Myeloma / pathology,  therapy*
Neoplasm Invasiveness / prevention & control
PTEN Phosphohydrolase / administration & dosage*,  genetics,  pharmacology
Treatment Outcome
Chemical
Reg. No./Substance:
EC 3.1.3.48/PTEN protein, human; EC 3.1.3.67/PTEN Phosphohydrolase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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