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

Hdl Handle:
http://hdl.handle.net/10147/206264
Title:
VHL genetic alteration in CCRCC does not determine de-regulation of HIF, CAIX, hnRNP A2/B1 and osteopontin.
Authors:
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
Affiliation:
University College Cork and Mercy University Hospital, Cork, Ireland.
Citation:
Anal Cell Pathol (Amst). 2010;33(3):121-32.
Journal:
Analytical cellular pathology (Amsterdam)
Issue Date:
31-Jan-2012
URI:
http://hdl.handle.net/10147/206264
DOI:
10.3233/ACP-CLO-2010-0541
PubMed ID:
20978319
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
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
ISSN:
2210-7185 (Electronic); 2210-7177 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorNyhan, Michelle Jen_GB
dc.contributor.authorEl Mashad, Shereen Men_GB
dc.contributor.authorO'Donovan, Tracey Ren_GB
dc.contributor.authorAhmad, Sarfrazen_GB
dc.contributor.authorCollins, Chrisen_GB
dc.contributor.authorSweeney, Paulen_GB
dc.contributor.authorRogers, Eamonnen_GB
dc.contributor.authorO'Sullivan, Gerald Cen_GB
dc.contributor.authorMcKenna, Sharon Len_GB
dc.date.accessioned2012-01-31T16:39:18Z-
dc.date.available2012-01-31T16:39:18Z-
dc.date.issued2012-01-31T16:39:18Z-
dc.identifier.citationAnal Cell Pathol (Amst). 2010;33(3):121-32.en_GB
dc.identifier.issn2210-7185 (Electronic)en_GB
dc.identifier.issn2210-7177 (Linking)en_GB
dc.identifier.pmid20978319en_GB
dc.identifier.doi10.3233/ACP-CLO-2010-0541en_GB
dc.identifier.urihttp://hdl.handle.net/10147/206264-
dc.description.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.en_GB
dc.language.isoengen_GB
dc.subject.meshAntigens, Neoplasm/*metabolismen_GB
dc.subject.meshBasic Helix-Loop-Helix Transcription Factors/*metabolismen_GB
dc.subject.meshBlotting, Westernen_GB
dc.subject.meshCarbonic Anhydrases/*metabolismen_GB
dc.subject.meshCarcinoma, Renal Cell/*genetics/*metabolismen_GB
dc.subject.meshCell Lineen_GB
dc.subject.meshHeterogeneous-Nuclear Ribonucleoprotein Group A-B/*metabolismen_GB
dc.subject.meshHumansen_GB
dc.subject.meshHypoxia-Inducible Factor 1, alpha Subunit/*metabolismen_GB
dc.subject.meshImmunohistochemistryen_GB
dc.subject.meshMutationen_GB
dc.subject.meshOsteopontin/*metabolismen_GB
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_GB
dc.subject.meshVon Hippel-Lindau Tumor Suppressor Protein/genetics/*metabolismen_GB
dc.titleVHL genetic alteration in CCRCC does not determine de-regulation of HIF, CAIX, hnRNP A2/B1 and osteopontin.en_GB
dc.contributor.departmentUniversity College Cork and Mercy University Hospital, Cork, Ireland.en_GB
dc.identifier.journalAnalytical cellular pathology (Amsterdam)en_GB
dc.description.provinceMunster-

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