RGD Reference Report - Upregulation of the insulin receptor and type I insulin-like growth factor receptor are early events in hepatocarcinogenesis. - Rat Genome Database

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Upregulation of the insulin receptor and type I insulin-like growth factor receptor are early events in hepatocarcinogenesis.

Authors: Aleem, E  Nehrbass, D  Klimek, F  Mayer, D  Bannasch, P 
Citation: Aleem E, etal., Toxicol Pathol. 2011 Apr;39(3):524-43. doi: 10.1177/0192623310396905. Epub 2011 Mar 16.
RGD ID: 10403043
Pubmed: PMID:21411721   (View Abstract at PubMed)
DOI: DOI:10.1177/0192623310396905   (Journal Full-text)

The molecular mechanisms underlying the development of hepatocellular carcinoma (HCC) are not yet fully understood. Preneoplastic foci of altered hepatocytes regularly precede HCC in various species. The predominant earliest type of foci of altered hepatocytes, the glycogen storage focus (GSF), shows an excess of glycogen (glycogenosis) in the cytoplasm. During progression from GSF to HCC, the stored glycogen is gradually reduced, resulting in complete loss in basophilic HCC. We have previously shown that in N-nitrosomorpholine-induced hepatocarcinogenesis, insulin receptor substrate (IRS-1) is strongly expressed in GSF and reduced during progression to HCC, thus correlating with the glycogen content. In the present study, we observed increased levels of insulin receptor, IGF-I receptor (IGF-IR), IRS-2, and mitogen-activated kinase/extracellular regulated kinase-1 in GSF, following the same pattern of expression as IRS-1. We conclude that the abundance of IRS-1, IRS-2, and mitogen-activated kinase/extracellular regulated kinase-1 coincides with a concerted upregulation of both IR and IGF-IR induced by the hepatocarcinogen. Our data suggest that in early hepatocellular preneoplasia, the upregulation of IR elicits glycogenosis through IRS-1 and/or IRS-2, whereas the increased level of the IGF-IR may lead to the increased cell proliferation previously reported in GSF. Therefore, the concerted upregulation of both IR and IGF-IR may represent initial events in hepatocarcinogenesis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pre-malignant neoplasm  ISOInsr (Rattus norvegicus)10403043; 10403043associated with Carcinoma and HepatocellularRGD 
pre-malignant neoplasm  IEP 10403043associated with Carcinoma and HepatocellularRGD 

Objects Annotated

Genes (Rattus norvegicus)
Insr  (insulin receptor)

Genes (Mus musculus)
Insr  (insulin receptor)

Genes (Homo sapiens)
INSR  (insulin receptor)


Additional Information