RGD Reference Report - Expression of iron regulatory genes in a rat model of hepatocellular carcinoma. - Rat Genome Database

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Expression of iron regulatory genes in a rat model of hepatocellular carcinoma.

Authors: Holmstrom, P  Gafvels, M  Eriksson, LC  Dzikaite, V  Hultcrantz, R  Eggertsen, G  Stal, P 
Citation: Holmstrom P, etal., Liver Int. 2006 Oct;26(8):976-85.
RGD ID: 2292036
Pubmed: PMID:16953838   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1478-3231.2006.01316.x   (Journal Full-text)

BACKGROUND/AIMS: The altered iron metabolism in hepatocellular carcinomas (HCCs), characterized by the iron-deficient phenotype, is suggested to be of importance for tumour growth. However, the underlying molecular mechanisms remain poorly understood. We asked whether these iron perturbations would involve altered expression of genes controlling iron homeostasis. METHODS: HCCs were induced in rats by the Solt and Farber protocol of chemical hepatocarcinogenesis, and to evaluate the effects of iron loading, one group of animals were supplemented with dietary iron during tumour progression. Tissue iron contents were determined, labelling indices of S-phase nuclei were calculated, and mRNA levels of iron-regulatory genes were quantitated. Protein levels of ferroportin1 were determined with Western blot. RESULTS: HCCs displayed reduced amount of tissue iron and lack of histologically stainable iron. HCCs expressed significantly higher mRNA levels of genes involved in iron uptake (transferrin receptor-1, divalent metal ion transporter-1), ferroxidase activity (Ferritin-H), and iron extrusion (ferroportin1). The protein levels of ferroportin1 in iron-deficient HCCs were similar as in control livers, and did not increase in HCCs exposed to iron. Hepcidin mRNA levels were decreased in iron-deficient HCCs, rose in response to iron loading and correlated to the tissue iron content. CONCLUSIONS: Taken together, the altered expressions of iron-regulatory genes in HCCs possibly reflect an increased demand for bioavailable iron and a high iron turnover in neoplastic cells.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hepatocellular carcinoma  ISOTfrc (Rattus norvegicus)2292036; 2292036mRNA:increased expression:liverRGD 
hepatocellular carcinoma  IEP 2292036mRNA:increased expression:liverRGD 

Objects Annotated

Genes (Rattus norvegicus)
Tfrc  (transferrin receptor)

Genes (Mus musculus)
Tfrc  (transferrin receptor)

Genes (Homo sapiens)
TFRC  (transferrin receptor)


Additional Information