RGD Reference Report - Altered expression of mitogen-activated protein kinases in a rat model of experimental hepatocellular carcinoma. - Rat Genome Database

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Altered expression of mitogen-activated protein kinases in a rat model of experimental hepatocellular carcinoma.

Authors: McKillop, I H  Schmidt, C M  Cahill, P A  Sitzmann, J V 
Citation: McKillop IH, etal., Hepatology. 1997 Dec;26(6):1484-91. doi: 10.1002/hep.510260615.
RGD ID: 150530477
Pubmed: PMID:9397988   (View Abstract at PubMed)
DOI: DOI:10.1002/hep.510260615   (Journal Full-text)

The mitogen-activated protein kinase (MAPK) cascade acts as a focal point for signal transduction following activation of both G-protein-linked and tyrosine kinase growth factor receptors. A common intermediate between both of these diverse receptor subtypes includes the small guanosine triphosphate (GTP)-binding protein, p21ras. Point mutations of p21ras have been identified in various tumor types and lead to constitutive activation of this protein and subsequent activation of downstream pathways including the MAPK cascade. Using an in vivo model of hepatocellular carcinoma (HCC), we investigated the abundance and function of individual components of the MAPK cascade and the presence of specific p21ras mutations in this model. Expression of components of the MAPK cascade were determined in tumor and adjacent, non-neoplastic liver specimens by Western blot analysis and functional activity confirmed by substrate phosphorylation assays. Mutations in p21ras were analyzed using an enzyme-linked immunosorbent assay. In tumor, extracellular regulated kinases (ERKs) ERK1, ERK2, and mitogen-activated ERK-regulated kinase-1 (MEK1) were elevated by three- to fourfold as compared with adjacent nontumorigenic normal liver. In contrast, MEK2 was elevated by only 28%. Substrate phosphorylation and detection of phosphorylated ERK1/2 proteins showed increased functional activity of these proteins of the same magnitude as that observed for protein expression. Mutations in p21ras were not detected in this experimental model of HCC. We conclude that HCC is associated with marked changes in expression and function of components of the MAPK cascade independent of common p21ras mutations.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hepatocellular carcinoma  ISOMap2k2 (Rattus norvegicus)150530477; 150530477protein:increased expression:liver and cytosol (rat)RGD 
hepatocellular carcinoma  IEP 150530477protein:increased expression:liver and cytosol (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Map2k2  (mitogen activated protein kinase kinase 2)

Genes (Mus musculus)
Map2k2  (mitogen-activated protein kinase kinase 2)

Genes (Homo sapiens)
MAP2K2  (mitogen-activated protein kinase kinase 2)


Additional Information