Document Detail

Hepatopoietin Cn suppresses apoptosis of human hepatocellular carcinoma cells by up-regulating myeloid cell leukemia-1.
MedLine Citation:
PMID:  20066738     Owner:  NLM     Status:  MEDLINE    
AIM: To investigate the role of hepatopoietin Cn (HPPCn) in apoptosis of hepatocellular carcinoma (HCC) cells and its mechanism.
METHODS: Two human HCC cell lines, SMMC7721 and HepG2, were used in this study. Immunostaining, Western blotting and enzyme linked immunosorbent assay were conducted to identify the expression of HPPCn and the existence of an autocrine loop of HPPCn/HPPCn receptor in SMMC7721 and HepG2. Apoptotic cells were detected using fluorescein isothiocyanate (FITC)-conjugated Annexin V and propidium iodide.
RESULTS: The HPPCn was highly expressed in human HCC cells and secreted into culture medium (CM). FITC-labeled recombinant human protein (rhHPPCn) could specifically bind to its receptor on HepaG2 cells. Treatment with 400 ng/mL rhHPPCn dramatically increased the viability of HCC-derived cells from 48.1% and 36.9% to 85.6% and 88.4%, respectively (P < 0.05). HPPCn silenced by small-interfering RNA reduced the expression and secretion of HPPCn and increased the apoptosis induced by trichostatin A. Additionally, HPPCn could up-regulate the expression of myeloid cell leukemia-1 (Mcl-1) in HCC cells via mitogen-activated protein kinase (MAPK) and sphingosine kinase-1.
CONCLUSION: HPPCn is a novel hepatic growth factor that can be secreted to CM and suppresses apoptosis of HCC cells by up-regulating Mcl-1 expression.
Jing Chang; Yang Liu; Dong-Dong Zhang; Da-Jin Zhang; Chu-Tse Wu; Li-Sheng Wang; Chun-Ping Cui
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  World journal of gastroenterology : WJG     Volume:  16     ISSN:  2219-2840     ISO Abbreviation:  World J. Gastroenterol.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-12     Completed Date:  2010-04-08     Revised Date:  2014-05-20    
Medline Journal Info:
Nlm Unique ID:  100883448     Medline TA:  World J Gastroenterol     Country:  China    
Other Details:
Languages:  eng     Pagination:  193-200     Citation Subset:  IM    
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MeSH Terms
Apoptosis / drug effects*
Carcinoma, Hepatocellular / metabolism,  pathology*
Cell Line, Tumor
Hepatocyte Growth Factor / metabolism,  pharmacology*
Hydroxamic Acids / pharmacology
Liver Neoplasms / metabolism,  pathology*
Mitogen-Activated Protein Kinase Kinases / metabolism
Myeloid Cell Leukemia Sequence 1 Protein
Phosphotransferases (Alcohol Group Acceptor) / metabolism
Protein Synthesis Inhibitors / pharmacology
Proto-Oncogene Proteins c-bcl-2 / metabolism*
Proto-Oncogene Proteins c-met / metabolism
Recombinant Proteins / pharmacology
Up-Regulation / drug effects*
Reg. No./Substance:
0/Hydroxamic Acids; 0/Myeloid Cell Leukemia Sequence 1 Protein; 0/Protein Synthesis Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 0/Recombinant Proteins; 3X2S926L3Z/trichostatin A; 67256-21-7/Hepatocyte Growth Factor; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.-/sphingosine kinase; EC Proteins c-met; EC Protein Kinase Kinases

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