Fibronectin is a hypoxia-independent target of the tumor suppressor VHL.
The von Hippel-Lindau (VHL) tumor suppressor gene regulates the extracellular matrix by controlling fibronectin deposition. To identify novel VHL target genes, we subjected mRNA from VHL-deficient RCC cells (786-0-pRC) and a transfectant re-expressing wildtype VHL (786-0-VHL) to differential expression profiling. Among the differentially expressed genes, we detected that fibronectin is upregulated in the presence of VHL, while it is not affected by hypoxia. Thus regulation of fibronectin deposition by VHL occurs at the transcriptional level, irrespective of oxygen levels.
Bluyssen
Hans A R
HA
Department of Medical Oncology, University Medical Center Utrecht, P.O. Box 85500, 3500 GA, Utrecht, The Netherlands.
Lolkema
Martijn P J K
MP
van Beest
Moniek
M
Boone
Michelle
M
Snijckers
Cristel M J T
CM
Los
Maartje
M
Gebbink
Martijn F B G
MF
Braam
Branko
B
Holstege
Frank C P
FC
Giles
Rachel H
RH
Voest
Emile E
EE
D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D002570:Ceruloplasmin / Q000096:biosynthesis / Q000235:genetics; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation; D042442:Vascular Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D005353:Fibronectins; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D042442:Vascular Endothelial Growth Factors; D002570:Ceruloplasmin; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human