Publication

VHL genetic alteration in CCRCC does not determine de-regulation of HIF, CAIX, hnRNP A2/B1 and osteopontin.

Nyhan, Michelle J
; 
El Mashad, Shereen M
; 
O'Donovan, Tracey R
; 
Ahmad, Sarfraz
; 
Collins, Chris
; 
Sweeney, Paul
; 
Rogers, Eamonn
; 
O'Sullivan, Gerald C
; 
McKenna, Sharon L
Author
Nyhan, Michelle J
 El Mashad, Shereen M
 O'Donovan, Tracey R
 Ahmad, Sarfraz
 Collins, Chris
 Sweeney, Paul
 Rogers, Eamonn
 O'Sullivan, Gerald C
 McKenna, Sharon L
Advisors
Editors
Other Contributors
Departments
University College Cork and Mercy University Hospital, Cork, Ireland.
Date
2012-01-31T16:39:18Z
Date Submitted
Keywords
Other Subjects
Subject Mesh
Antigens, Neoplasm/*metabolism
Basic Helix-Loop-Helix Transcription Factors/*metabolism
Blotting, Western
Carbonic Anhydrases/*metabolism
Carcinoma, Renal Cell/*genetics/*metabolism
Cell Line
Heterogeneous-Nuclear Ribonucleoprotein Group A-B/*metabolism
Humans
Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
Immunohistochemistry
Mutation
Osteopontin/*metabolism
Reverse Transcriptase Polymerase Chain Reaction
Von Hippel-Lindau Tumor Suppressor Protein/genetics/*metabolism
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
URI
https://hdl.handle.net/10147/206264
Abstract
BACKGROUND: von Hippel-Lindau (VHL) tumour suppressor gene inactivation is associated with clear cell renal cell carcinoma (CCRCC) development. The VHL protein (pVHL) has been proposed to regulate the expression of several proteins including Hypoxia Inducible Factor-alpha (HIF-alpha), carbonic anhydrase (CA)IX, heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 and osteopontin. pVHL has been characterized in vitro, however, clinical studies are limited. We evaluated the impact of VHL genetic alterations on the expression of several pVHL protein targets in paired normal and tumor tissue. METHODS: The VHL gene was sequenced in 23 CCRCC patients and VHL transcript levels were evaluated by real-time RT-PCR. Expression of pVHL's protein targets were determined by Western blotting in 17 paired patient samples. RESULTS: VHL genetic alterations were identified in 43.5% (10/23) of CCRCCs. HIF-1alpha, HIF-2alpha and CAIX were up-regulated in 88.2% (15/17), 100% (17/17) and 88.2% (15/17) of tumors respectively and their expression is independent of VHL status. hnRNP A2/B1 and osteopontin expression was variable in CCRCCs and had no association with VHL genetic status. CONCLUSION: As expression of these proposed pVHL targets can be achieved independently of VHL mutation (and possibly by hypoxia alone), these data suggests that other pVHL targets may be more crucial in renal carcinogenesis.
Language
eng
Citation
Anal Cell Pathol (Amst). 2010;33(3):121-32.
ISSN
2210-7185 (Electronic)
2210-7177 (Linking)
eISSN
ISBN
DOI
10.3233/ACP-CLO-2010-0541
PMID
20978319
PMCID
Sponsorships
Funding Sources
Funding Amounts
Grant Identifiers
Methodology
Duration
Ethical Approval