VHL genetic alteration in CCRCC does not determine de-regulation of HIF, CAIX, hnRNP A2/B1 and osteopontin.
AuthorsNyhan, Michelle J
El Mashad, Shereen M
O'Donovan, Tracey R
O'Sullivan, Gerald C
McKenna, Sharon L
AffiliationUniversity College Cork and Mercy University Hospital, Cork, Ireland.
Basic Helix-Loop-Helix Transcription Factors/*metabolism
Carcinoma, Renal Cell/*genetics/*metabolism
Heterogeneous-Nuclear Ribonucleoprotein Group A-B/*metabolism
Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
Reverse Transcriptase Polymerase Chain Reaction
Von Hippel-Lindau Tumor Suppressor Protein/genetics/*metabolism
MetadataShow full item record
CitationAnal Cell Pathol (Amst). 2010;33(3):121-32.
JournalAnalytical cellular pathology (Amsterdam)
AbstractBACKGROUND: 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.
- VHL genetic alteration in CCRCC does not determine de-regulation of HIF, CAIX, hnRNP A2/B1 and osteopontin.
- Authors: Nyhan MJ, El Mashad SM, O'Donovan TR, Ahmad S, Collins C, Sweeney P, Rogers E, O'Sullivan GC, McKenna SL
- Issue date: 2011 Jun
- The VHL-dependent regulation of microRNAs in renal cancer.
- Authors: Neal CS, Michael MZ, Rawlings LH, Van der Hoek MB, Gleadle JM
- Issue date: 2010 Oct 21
- [The expression of hypoxia inducible factor-1,2 alpha in sporadic clear cell renal cell carcinoma and their relationships to the mutations of von Hippel-Lindau gene].
- Authors: Gong K, Zhang N, Na X, Wu G, Yang XY, Xin DQ, Na YQ
- Issue date: 2005 Mar 15
- The relationship of erythropoietin overexpression with von Hippel-Lindau tumour suppressor gene mutations between hypoxia-inducible factor-1α and -2α in sporadic clear cell renal carcinoma.
- Authors: Gong K, Zhang N, Zhang K, Na Y
- Issue date: 2010 Dec
- The von Hippel-Lindau tumor suppressor protein regulates gene expression and tumor growth through histone demethylase JARID1C.
- Authors: Niu X, Zhang T, Liao L, Zhou L, Lindner DJ, Zhou M, Rini B, Yan Q, Yang H
- Issue date: 2012 Feb 9