Transferrin receptor expression in rat liver: Immunohistochemical and biochemical analysis of the effect of age and iron storage

Sciot, Raf; Verhoeven, Guido; Eyken, Peter Van; Ćailleau, Jean; Desmet, Valeer

doi:10.1002/hep.1840110313

Cited by 25 publications

(14 citation statements)

References 43 publications

(22 reference statements)

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“…By using 89 Zr-desferrioxamine-labeled transferrin ( 89 Zr-transferrin), a new positron emission tomography (PET) radiotracer that binds TFRC (Holland et al 2012), it is possible to indirectly assess MYC activity in vivo. HepG2 and Alexander cell lines were implanted subcutaneously, as the TFRC levels in the liver are already high via MYC-independent mechanisms (Sciot et al 1990). Upon tumor formation, mice were treated with PHA-767491 during 3 d, and PET was performed 2 d after.…”

Section: Cdk9 Mediates Transcription Elongation Of Myc Targets In Mycmentioning

confidence: 99%

CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma

et al. 2014

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One-year survival rates for newly diagnosed hepatocellular carcinoma (HCC) are <50%, and unresectable HCC carries a dismal prognosis owing to its aggressiveness and the undruggable nature of its main genetic drivers. By screening a custom library of shRNAs directed toward known drug targets in a genetically defined Myc-driven HCC model, we identified cyclin-dependent kinase 9 (Cdk9) as required for disease maintenance. Pharmacological or shRNA-mediated CDK9 inhibition led to robust anti-tumor effects that correlated with MYC expression levels and depended on the role that both CDK9 and MYC exert in transcription elongation. Our results establish CDK9 inhibition as a therapeutic strategy for MYC-overexpressing liver tumors and highlight the relevance of transcription elongation in the addiction of cancer cells to MYC.

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Section: Cdk9 Mediates Transcription Elongation Of Myc Targets In Mycmentioning

confidence: 99%

CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma

et al. 2014

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“…Hepatic expression of the TfR has been reported to be up-regulated in rodent models of dietary iron deficiency and down-regulated by dietary iron loading (20,21). To determine whether TfR2 expression is regulated by iron status, we analyzed TfR2 mRNA in control, iron-deficient, and iron-loaded mice.…”

Section: Effect Of Iron Status On Tfr2 Mrna In Livermentioning

confidence: 99%

Transferrin receptor 2: Continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis

Fleming

Migas

Holden

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

243

164

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Hereditary hemochromatosis (HH) is a common autosomal recessive disorder characterized by excess absorption of dietary iron and progressive iron deposition in several tissues, particularly liver. Liver disease resulting from iron toxicity is the major cause of death in HH. Hepatic iron loading in HH is progressive despite downregulation of the classical transferrin receptor (TfR). Recently a human cDNA highly homologous to TfR was identified and reported to encode a protein (TfR2) that binds holotransferrin and mediates uptake of transferrin-bound iron. We independently identified a full-length murine EST encoding the mouse orthologue of the human TfR2. Although homologous to murine TfR in the coding region, the TfR2 transcript does not contain the ironresponsive elements found in the 3 untranslated sequence of TfR mRNA. To determine the potential role for TfR2 in iron uptake by liver, we investigated TfR and TfR2 expression in normal mice and murine models of dietary iron overload (2% carbonyl iron), dietary iron deficiency (gastric parietal cell ablation), and HH (HFE ؊͞؊).Northern blot analyses demonstrated distinct tissue-specific patterns of expression for TfR and TfR2, with TfR2 expressed highly only in liver where TfR expression is low. In situ hybridization demonstrated abundant TfR2 expression in hepatocytes. In contrast to TfR, TfR2 expression in liver was not increased in iron deficiency. Furthermore, hepatic expression of TfR2 was not downregulated with dietary iron loading or in the HFE ؊͞؊ model of HH. From these observations, we propose that TfR2 allows continued uptake of Tf-bound iron by hepatocytes even after TfR has been down-regulated by iron overload, and this uptake contributes to the susceptibility of liver to iron loading in HH.

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“…For example, histochemical analysis of the TfR has been used to locate nasopharyngeal carcinoma [162], to detect glioblastoma multiforme [163], to differentiate between benign and malignant liver tumors [164], to assess the proliferative index of breast carcinoma [165] and to provide a survival-predictive value of various forms of lung cancers [166]. In addition, TfR induction in activated lymphocytes is also commonly employed as a reference for monitoring lymphoproliferative disorders [167].…”

Section: Tfr As a Clinical Diagnostic Toolmentioning

confidence: 99%

Regulation of Transferrin Function and Expression: Review and Update

Lok¹,

Loh²

1998

Biol Signals Recept

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The cellular iron uptake is a precisely controlled process to fulfill the iron demand for the synthesis and functions of a variety of iron-containing proteins, and one of the main molecules involved is the transferrin receptor (TfR), which mediates the uptake process via the transferrin cycle. The TfR expression is tightly regulated by factors such as intracellular iron level, cell proliferation or erythropoiesis at levels of receptor recycling, transcriptional or posttranscriptional control. The iron-regulatory protein/iron-responsive element system has been widely used to explain changes in receptor expression during iron loading or depletion, oxidative stress and nitric oxide stimulation. On the other hand, transcriptional control of TfR expression appears to be more important in erythroid differentiation and general cell proliferation. There is also an increasing awareness of the clinical application and experimental therapeutics based on the TfR functioning and expression. In this review, we attempt to provide a concise account of the studies of TfR structure and function as well as those areas that have not been reviewed in depth, in particular, tissue-specific regulation of TfR, the molecular mechanisms of TfR expression, and the use of TfR as diagnostic and therapeutic tools. The regulation of TfR expression in various tissues is related to its specific cellular iron requirements. Hemoglobin-synthesizing cells exhibit distinct features of iron metabolism and TfR expression as compared to most non-erythroid cells which synthesize a much lower amount of heme. For most non-erythroid cells, iron can regulate the TfR expression in a reciprocal manner through modulating the stability of the receptor mRNA whereas in hemoglobin-synthesizing cells, the TfR expression is independent of the cellular iron loading. In spite of a wide heterogeneity in the way receptor redistribution is in response to various stimuli, regulation of the constitutive expression of TfR is one of the ways of regulating the cellular iron uptake. This expression operates on both transcriptional and posttranscriptional levels. In general, factors related to cell growth and differentiation operate on the gene transcription level, whereas iron regulates the fate of the mature mRNA.

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Transferrin receptor expression in rat liver: Immunohistochemical and biochemical analysis of the effect of age and iron storage

Cited by 25 publications

References 43 publications

CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma

CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma

Transferrin receptor 2: Continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis

Regulation of Transferrin Function and Expression: Review and Update

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