Document Detail


RNAi-mediated CD73 suppression induces apoptosis and cell-cycle arrest in human breast cancer cells.
MedLine Citation:
PMID:  20874842     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ecto-5'-nucleotidase (CD73), a cell surface protein that hydrolyzes extracellular AMP into adenosine and phosphate, is overexpressed in many solid tumors. In this study, we tested the hypothesis that increased CD73 may promote tumor progression by examining the effect of CD73 suppression via RNA interference and CD73 overexpression on tumor growth in vivo and in vitro. Using digitized whole-body images, plate clone forming assay and TUNEL assay in frozen tissue sections, we found that the cell growth rate was significantly lower in vivo and in vitro after CD73 suppression and late apoptosis was much higher in xenograft tumors developed from the CD73-siRNA transfected MB-MDA-231 clone (P1). By flow cytometry, the P1 cell cycle was arrested in the G0/G1 phase. Moreover, Bcl-2 was downregulated, while Bax and caspase-3 were upregulated with CD73 suppression. CD73 inhibitor α,β-methylene adenosine-5'-disphosphate (APCP) functioned similarly with RNAi-mediated CD73 suppression. In addition, in transfected MCF-7 cells, we found that CD73 overexpression increased cell viability and promoted cell cycle progression, depending on its enzyme activity. More intriguingly, CD73 overexpression in MCF-7 breast cancer cells produces a tumorigenic phenotype. We conclude that CD73 plays an important role in breast cancer growth by affecting cell cycle progression and apoptosis.
Authors:
Xiuling Zhi; Yingjian Wang; Xuerui Zhou; Jerry Yu; Rongrong Jian; Shaoxian Tang; Lianhua Yin; Ping Zhou
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-28
Journal Detail:
Title:  Cancer science     Volume:  101     ISSN:  1349-7006     ISO Abbreviation:  Cancer Sci.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-16     Completed Date:  2010-12-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101168776     Medline TA:  Cancer Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  2561-9     Citation Subset:  IM    
Copyright Information:
© 2010 Japanese Cancer Association.
Affiliation:
Department of Physiology and Pathophysiology, Shanghai Medical College, Shanghai, China.
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MeSH Terms
Descriptor/Qualifier:
5'-Nucleotidase / biosynthesis*,  genetics
Animals
Apoptosis / physiology*
Blotting, Western
Breast Neoplasms / genetics,  metabolism*
Cell Cycle / physiology*
Cell Line, Tumor
Cell Separation
Female
Flow Cytometry
Humans
Immunohistochemistry
In Situ Nick-End Labeling
Mice
Mice, Nude
RNA, Small Interfering / genetics*
Reverse Transcriptase Polymerase Chain Reaction
Tissue Array Analysis
Transfection
Chemical
Reg. No./Substance:
0/RNA, Small Interfering; EC 3.1.3.5/5'-Nucleotidase

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