Document Detail

CDC25A inhibition suppresses the growth and invasion of human hepatocellular carcinoma cells.
MedLine Citation:
PMID:  18204780     Owner:  NLM     Status:  MEDLINE    
CDC25A is a cell cycle-activating phosphatase that promotes transition from the G1 to S phase. We previously reported that overexpression of CDC25A in human hepatocellular carcinoma (HCC) tissue samples was associated with poor prognosis. In this study, we attempted suppression of CDC25A in HCC cells to elucidate the therapeutic potential of this approach. Administration of CDC25A antisense (AS) oligonucleotide resulted in 25-50% inhibition of cell growth at 48 h, G0-G1 arrest, and significant inhibition of cancer cell invasion. To elucidate the underlying mechanism of the inhibitory effects of HCC cell invasion, we examined several invasion-associated molecules, and we found that membrane-type 3 (MT3)-matrix metalloproteinase (MMP) mRNA was greatly reduced following treatment with AS oligonucleotide to CDC25A or siRNA treatment. Notably, screening of a panel of gastrointestinal cancer cells indicated that MT3-MMP was generally expressed by HCC cells, whereas other cell types did not express this type of matrix metalloproteinase so frequently. We also found that CDC25A facilitated cellular differentiation by increasing albumin expression in the PLC cell line. These results suggest that CDC25A, by inhibiting HCC growth and invasion, may be a feasible therapeutic target for human HCC.
Xundi Xu; Hirofumi Yamamoto; Guoxing Liu; Yasuhiro Ito; Chew Yee Ngan; Motoi Kondo; Hiroaki Nagano; Keizo Dono; Mitsugu Sekimoto; Morito Monden
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of molecular medicine     Volume:  21     ISSN:  1107-3756     ISO Abbreviation:  Int. J. Mol. Med.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-21     Completed Date:  2008-03-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9810955     Medline TA:  Int J Mol Med     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  145-52     Citation Subset:  IM    
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
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MeSH Terms
Albumins / genetics,  metabolism
Carcinoma, Hepatocellular / enzymology*,  genetics,  pathology*
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Gene Expression Regulation, Neoplastic / drug effects
Liver Neoplasms / enzymology*,  genetics,  pathology*
Matrix Metalloproteinases / genetics,  metabolism
Neoplasm Invasiveness
Oligonucleotides, Antisense / pharmacology
RNA, Small Interfering / pharmacology
cdc25 Phosphatases / antagonists & inhibitors*
Reg. No./Substance:
0/Albumins; 0/Oligonucleotides, Antisense; 0/RNA, Small Interfering; 3326-32-7/Fluorescein-5-isothiocyanate; EC Phosphatases; EC 3.4.24.-/Matrix Metalloproteinases

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