RGD Reference Report - Effect of hepatocyte growth factor on methionine adenosyltransferase genes and growth is cell density-dependent in HepG2 cells. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Effect of hepatocyte growth factor on methionine adenosyltransferase genes and growth is cell density-dependent in HepG2 cells.

Authors: Yang, H  Magilnick, N  Noureddin, M  Mato, JM  Lu, SC 
Citation: Yang H, etal., J Cell Physiol. 2007 Mar;210(3):766-73.
RGD ID: 2317575
Pubmed: PMID:17154373   (View Abstract at PubMed)
DOI: DOI:10.1002/jcp.20891   (Journal Full-text)

Hepatocyte growth factor (HGF) is a potent hepatocyte mitogen but its effect in liver cancer is conflicting. Methionine adenosyltransferase (MAT) is an essential enzyme encoded by two genes (MAT1A and MAT2A), while a third gene (MAT2beta) encodes for a subunit that regulates the MAT2A-encoded isoenzyme. MAT1A is silenced while MAT2A and MAT2beta are induced in hepatocellular carcinoma (HCC). The current work examined expression of HGF/c-met in HCC and whether HGF regulates MAT genes and growth in HepG2 cells. We found the mRNA levels of HGF and c-met are markedly increased in HCC. To study the influence of cell density, HepG2 cells were plated under high-density (HD) or low-density (LD) and treated with HGF (10 ng/ml). Cell density had a dramatic effect on MAT1A expression, being nearly undetectable at LD to a ninefold induction under HD. Cell density also determined the effect of HGF. At HD, HGF increased the mRNA levels of p21 and p27, while lowering the levels of MAT genes, cyclin A, and c-met. At LD, HGF increased the mRNA levels of cyclin A, MAT2A, MAT2beta, and c-met. Consistently, HGF inhibits growth under HD but stimulates growth under LD. HGF induced sustained high ERK activation under HD as compared to LD. In summary, HGF induces genes favoring growth and is mitogenic when HepG2 cells are plated under LD; however, the opposite occurs under HD. This involves cell density-dependent differences in HGF-induced ERK activation. This may explain why HGF is mitogenic only when there is loss of cell-cell contact in vivo.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hepatocellular carcinoma  IEP 2317575mRNA:increased expression:liver and carcinoma (human)RGD 
hepatocellular carcinoma  ISOMET (Homo sapiens)2317575; 2317575mRNA:increased expression:liver and carcinoma (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Met  (MET proto-oncogene, receptor tyrosine kinase)

Genes (Mus musculus)
Met  (met proto-oncogene)

Genes (Homo sapiens)
MET  (MET proto-oncogene, receptor tyrosine kinase)


Additional Information