Ferritin as an endogenous MRI reporter for noninvasive imaging of gene expression in C6 glioma tumors

被引:259
作者
Cohen, B
Dafni, H
Meir, G
Harmelin, A
Neeman, M [1 ]
机构
[1] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel
[2] Weizmann Inst Sci, Dept Vet Resources, IL-76100 Rehovot, Israel
来源
NEOPLASIA | 2005年 / 7卷 / 02期
基金
以色列科学基金会;
关键词
MRI; gene expression; ferritin; iron; C6; glioma;
D O I
10.1593/neo.04436
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The heavy chain of murine ferritin, an iron storage molecule with ferroxidase activity, was developed as a novel endogenous reporter for the detection of gene expression by magnetic resonance imaging (MRI). Expression of both enhanced green fluorescent protein (EGFP) and influenza hemagglutinin (HA)-tagged ferritin were tightly coregulated by tetracycline (TET), using a bidirectional expression vector. C6 cells stably expressing a TET-EGFP-HA-ferritin construct enabled the dynamic detection of TET-regulated gene expression by MRI, followed by independent validation using fluorescence microscopy and histology. MR relaxation rates were significantly elevated both in vitro and in vivo on TET withdrawal, and were consistent with induced expression of ferritin and increase in intracellular iron content. Hence, overexpression of ferritin was sufficient to trigger cellular response, augmenting iron uptake to a degree detectable by MRI. Application of this novel MR reporter gene that generates significant contrast in the absence of exogenously administered substrates opens new possibilities for noninvasive molecular imaging of gene expression by MRI.
引用
收藏
页码:109 / 117
页数:9
相关论文
共 33 条
[1]   In vitro MR imaging of regulated gene expression [J].
Alfke, H ;
Stöppler, H ;
Nocken, F ;
Heverhagen, JT ;
Kleb, B ;
Czubayko, F ;
Klose, KJ .
RADIOLOGY, 2003, 228 (02) :488-492
[2]   MRI of the liver and the pituitary gland in patients with β-thalassemia major:: Does hepatic siderosis predict pituitary iron deposition? [J].
Argyropoulou, MI ;
Kiortsis, DN ;
Efremidis, SC .
EUROPEAN RADIOLOGY, 2003, 13 (01) :12-16
[3]  
Artemov D, 2003, CANCER RES, V63, P2723
[4]  
Bartzokis G, 2000, CELL MOL BIOL, V46, P821
[5]   FIELD-DEPENDENT TRANSVERSE RELAXATION RATE INCREASE MAY BE A SPECIFIC MEASURE OF TISSUE IRON STORES [J].
BARTZOKIS, G ;
ARAVAGIRI, M ;
OLDENDORF, WH ;
MINTZ, J ;
MARDER, SR .
MAGNETIC RESONANCE IN MEDICINE, 1993, 29 (04) :459-464
[6]   IRON INCORPORATION INTO FERRITINS - EVIDENCE FOR THE TRANSFER OF MONOMERIC FE(III) BETWEEN FERRITIN MOLECULES AND FOR THE FORMATION OF AN UNUSUAL MINERAL IN THE FERRITIN OF ESCHERICHIA-COLI [J].
BAUMINGER, ER ;
TREFFRY, A ;
HUDSON, AJ ;
HECHEL, D ;
HODSON, NW ;
ANDREWS, SC ;
LEVI, S ;
NOWIK, I ;
AROSIO, P ;
GUEST, JR ;
HARRISON, PM .
BIOCHEMICAL JOURNAL, 1994, 302 :813-820
[7]   IRON (II) OXIDATION AND EARLY INTERMEDIATES OF IRON-CORE FORMATION IN RECOMBINANT HUMAN H-CHAIN FERRITIN [J].
BAUMINGER, ER ;
HARRISON, PM ;
HECHEL, D ;
HODSON, NW ;
NOWIK, I ;
TREFFRY, A ;
YEWDALL, SJ .
BIOCHEMICAL JOURNAL, 1993, 296 :709-719
[8]   CYTOTOXICITY OF METALS, METAL-METAL AND METAL-CHELATOR COMBINATIONS ASSAYED INVITRO [J].
BORENFREUND, E ;
PUERNER, JA .
TOXICOLOGY, 1986, 39 (02) :121-134
[9]   ALTERING CREATINE-KINASE ISOENZYMES IN TRANSGENIC MOUSE MUSCLE BY OVEREXPRESSION OF THE B-SUBUNIT [J].
BROSNAN, MJ ;
RAMAN, SP ;
CHEN, LH ;
KORETSKY, AP .
AMERICAN JOURNAL OF PHYSIOLOGY, 1993, 264 (01) :C151-C160
[10]   Overexpression of wild type and mutated human ferritin H-chain in HeLa cells -: In vivo role of ferritin ferroxidase activity [J].
Cozzi, A ;
Corsi, B ;
Levi, S ;
Santambrogio, P ;
Albertini, A ;
Arosio, P .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (33) :25122-25129