Document Detail


The role of c-Myb and Sp1 in the up-regulation of methionine adenosyltransferase 2A gene expression in human hepatocellular carcinoma.
MedLine Citation:
PMID:  11427482     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Liver-specific and non-liver-specific methionine adenosyltransferase (MAT) are products of two genes, MAT1A and MAT2A, respectively, that catalyze the formation of S-adenosylmethionine. We showed a switch from MAT1A to MAT2A expression at the transcriptional level in human hepatocellular carcinoma (HCC) that facilitates cancer cell growth. The purpose of the present study was to better understand the molecular mechanism of increased MAT2A expression in HCC. In vitro DNase I footprinting analysis revealed two protected sites (-354 to -312 and -73 to -28) using nuclear proteins from HCC and HepG2 cells, but not normal liver. These sites are also protected in HepG2 cells on in vivo DNase I footprinting analysis. These protected sites contain consensus binding sites for c-Myb and Sp1. In HCC, the mRNA levels of c-myb and Sp1 and binding to their respective sites increased. Mutation of the c-Myb or Sp1 site reduced MAT2A promoter activity by 67% and 50%, respectively. The importance of these cis-acting elements and trans-activating factors was confirmed using heterologous promoter and expression vectors. Increased expression of c-Myb and Sp1 and binding to the MAT2A promoter contribute to transcriptional up-regulation of MAT2A in HCC.-Yang, H., Huang, Z.-Z., Wang, J., Lu, S. C. The role of c-Myb and Sp1 in the up-regulation of methionine adenosyltransferase 2A gene expression in human hepatocellular carcinoma.
Authors:
H Yang; Z Z Huang; J Wang; S C Lu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  15     ISSN:  0892-6638     ISO Abbreviation:  FASEB J.     Publication Date:  2001 Jul 
Date Detail:
Created Date:  2001-06-27     Completed Date:  2001-07-26     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1507-16     Citation Subset:  IM    
Affiliation:
Division of Gastroenterology and Liver Diseases, USC Liver Disease Research Center, USC-UCLA Research Center for Alcoholic Liver and Pancreatic Diseases, Keck School of Medicine USC, Los Angeles, California 90033, USA.
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MeSH Terms
Descriptor/Qualifier:
Carcinoma, Hepatocellular / enzymology,  genetics*
DNA Footprinting
Deoxyribonuclease I / metabolism
Gene Expression Regulation, Enzymologic
Humans
Liver / enzymology,  metabolism
Liver Neoplasms / enzymology,  genetics*
Methionine Adenosyltransferase / biosynthesis,  genetics*
Promoter Regions, Genetic / genetics,  physiology
Proto-Oncogene Proteins c-myb / physiology*
Sp1 Transcription Factor / physiology*
Transcription, Genetic*
Tumor Cells, Cultured
Up-Regulation
Grant Support
ID/Acronym/Agency:
DK48522/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-myb; 0/Sp1 Transcription Factor; EC 2.5.1.6/Methionine Adenosyltransferase; EC 3.1.21.1/Deoxyribonuclease I

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


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