TGFBI-promoted adhesion, migration and invasion of human renal cell carcinoma depends on inactivation of von Hippel-Lindau tumor suppressor.

Abstract

OBJECTIVE:

To investigate the role of transforming growth factor-β-induced (TGFBI) in metastasis of renal cell carcinoma (RCC) and the associations between TGFBI expression and von Hippel-Lindau (VHL) status.

METHODS:

In null type VHL cells stably transfected with the VHL vector, the expression of VHL in cells with wild type VHL was decreased by siRNA. We investigated the effects of hypoxia-inducible transcription factor (HIF) on TGFBI in RCC cells by decreasing the expression levels of HIF-1α and HIF-2α through siRNA. The secretion of transforming growth factor-β1 (TGF-β1) in RCC cells with different VHL status was analyzed by enzyme-linked immunosorbent assay. The role of TGFBI in metastasis and the effect of VHL activation on TGFBI-induced adhesion, migration, and invasion in RCC cells were examined using matrigel, chemotaxis, and the transwell system, respectively.

RESULTS:

Our results suggested that TGF-β1 and TGFBI might be targets of VHL, and the suppression of TGFBI by VHL is not by way of the HIF-1α or HIF-2α pathway. The expression of TGFBI was significantly enhanced by TGF-β1 in VHL-inactive RCC cells compared with VHL-active cells. In addition, these results indicate that TGFBI participated in the adhesion, migration, and invasion of RCC cells, which are dependent on the inactivation of VHL.

CONCLUSION:

The results of the present study suggest that TGFBI-promoted metastasis of RCC cells depends on inactivation of the VHL tumor suppressor and that TGFBI could be a therapeutic target against RCC in the future.

• Authors: Donghao Shang, Yuting Liu, Peiqian Yang, Yongqian Chen, Ye Tian
• Journal: Urology (Urology) Vol. 79 Issue 4 Pg. 966.e1-7 (Apr 2012) ISSN: 1527-9995 [Electronic] United States
• PMID: 22341602 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• Hypoxia-Inducible Factor 1, alpha Subunit
• RNA, Small Interfering
• Transforming Growth Factor beta1
• endothelial PAS domain-containing protein 1
• Von Hippel-Lindau Tumor Suppressor Protein

Topics

• Basic Helix-Loop-Helix Transcription Factors (physiology)
• Blotting, Western
• Carcinoma, Renal Cell (genetics, physiopathology, secondary)
• Cell Adhesion (physiology)
• Cell Migration Assays
• Cell Movement (physiology)
• Down-Regulation (physiology)
• Gene Expression Regulation, Neoplastic (physiology)
• Gene Silencing
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (physiology)
• Kidney Neoplasms (genetics, pathology, physiopathology)
• Neoplasm Invasiveness
• RNA, Small Interfering
• Reverse Transcriptase Polymerase Chain Reaction
• Transforming Growth Factor beta1 (physiology)
• Von Hippel-Lindau Tumor Suppressor Protein (genetics, physiology)