Titre du document / Document title

von Hippel Lindau tumor suppressor regulates hepatic glucose metabolism by controlling expression of glucose transporter 2 and glucose 6-phosphatase

Auteur(s) / Author(s)

PARK Sang-Ki ^{(1 2)} ; HAASE Volker H. ⁽³⁾ ; JOHNSON Randall S. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0366, ETATS-UNIS
⁽²⁾ Department of Pharmaceutical Sciences, St. John's University, Queens, NY 11439, ETATS-UNIS
⁽³⁾ Renal-Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6144, ETATS-UNIS

Résumé / Abstract

von Hippel Lindau (VHL) disease is a hereditary cancer syndrome caused by biallelic inactivation of the VHL tumor suppressor gene. The most widely known function of VHL is to limit normoxic protein expression of hypoxia-inducible factor-a (HIF-a). Loss of the functional VHL gene causes constitutive stabilization of HIF-a that primarily up-regulates hypoxia-inducible genes even at normal oxygen concentration, which in turn contribute to VHL tumor progression. We report on the novel function of VHL in hepatic glucose storage and disposal. VHL deletion in adult mouse liver quickly leads to increased accumulation of glycogen granules as well as lipid droplets. This abnormal glycogen storage in VHL-inactivated liver arises at least in part from significantly reduced expression of two key liver-specific glucose metabolism genes, glucose transporter-2 (GLUT2) and glucose-6-phosphatase (G-6-Pase). The expression pattern of these genes in VHL knock-out liver was in contrast to that of well-known HIF target genes, such as PGK, Glut-1, VEGF, and EPO, all of which are highly elevated upon VHL inactivation. Our findings suggest that two distinct signaling pathways exist at the downstream of VHL controlling different sets of gene expression. Following VHL inactivation, one pathway causes oxygen-independent overexpression of classic hypoxia-inducible genes and the other one described here suppresses expression of the genes important for liver glucose metabolism.

Revue / Journal Title

International journal of oncology   ISSN 1019-6439 

Source / Source

2007, vol. 30, n^o2, pp. 341-348 [8 page(s) (article)] (36 ref.)

Langue / Language

Anglais

Editeur / Publisher

Editorial Academy of the International Journal of Oncology, Athens, GRECE  (1992) (Revue)

Mots-clés anglais / English Keywords

Digestive system ; GLUT1 glucose transporter ; Cancerology ; Gene expression ; Tumor cell ; Biological transport ; Metabolism ; Glucose ; Liver ; Tumor suppressor gene ;

Mots-clés français / French Keywords

Appareil digestif ; Transporteur GLUT1 ; Cancérologie ; Expression génique ; Cellule tumorale ; Transport biologique ; Métabolisme ; Glucose ; Foie ; Gène suppresseur tumeur ;

Mots-clés espagnols / Spanish Keywords

Aparato digestivo ; Cancerología ; Expresión genética ; Célula tumoral ; Transporte biológico ; Metabolismo ; Glucosa ; Hígado ; Gen supresor tumor ;

Mots-clés d'auteur / Author Keywords

pVHL ; HIF ; glycogen ; tumor cell metabolism ; gene expression ;

Localisation / Location

INIST-CNRS, Cote INIST : 26333, 35400014536735.0060