P53 suppresses expression of the 14-3-3gamma oncogene

Persistent Link:
http://hdl.handle.net/10150/610345
Title:
P53 suppresses expression of the 14-3-3gamma oncogene
Author:
Radhakrishnan, Vijayababu; Putnam, Charles; Qi, Wenqing; Martinez, Jesse
Affiliation:
Arizona Cancer Center, Department of Cellular & Molecular Medicine, University of Arizona, Tucson, Arizona 85724, USA; Department of Pediatrics, Steele Research Center, 1501 N Campbell Ave, Tucson, Arizona 85724, USA; Department of Surgery, 1501 N Campbell ave, Tucson, Arizona 85724, USA; Department of Medicine, 1515 N. Campbell Ave., Tucson, Arizona 85724, USA
Issue Date:
2011
Publisher:
BioMed Central
Citation:
Radhakrishnan et al. BMC Cancer 2011, 11:378 http://www.biomedcentral.com/1471-2407/11/378
Journal:
BMC Cancer
Rights:
© 2011 Radhakrishnan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
BACKGROUND:14-3-3 proteins are a family of highly conserved proteins that are involved in a wide range of cellular processes. Recent evidence indicates that some of these proteins have oncogenic activity and that they may promote tumorigenesis. We previously showed that one of the 14-3-3 family members, 14-3-3gamma, is over expressed in human lung cancers and that it can induce transformation of rodent cells in vitro.METHODS:qRTPCR and Western blot analysis were performed to examine 14-3-3gamma expression in non-small cell lung cancers (NSCLC). Gene copy number was analyzed by qPCR. P53 mutations were detected by direct sequencing and also by western blot. CHIP and yeast one hybrid assays were used to detect p53 binding to 14-3-3gamma promoter.RESULTS:Quantitative rtPCR results showed that the expression level of 14-3-3gamma was elevated in the majority of NSCLC that we examined which was also consistent with protein expression. Further analysis of the expression pattern of 14-3-3gamma in lung tumors showed a correlation with p53 mutations suggesting that p53 might suppress 14-3-3 gamma expression. Analysis of the gamma promoter sequence revealed the presence of a p53 consensus binding motif and in vitro assays demonstrated that wild-type p53 bound to this motif when activated by ionizing radiation. Deletion of the p53 binding motif eliminated p53's ability to suppress 14-3-3gamma expression.CONCLUSION:Increased expression of 14-3-3gamma in lung cancer coincides with loss of functional p53. Hence, we propose that 14-3-3gamma's oncogenic activities cooperate with loss of p53 to promote lung tumorigenesis.
EISSN:
 1471-2407
DOI:
10.1186/1471-2407-11-378
Keywords:
Lung cancer; 14-3-3; p53 mutations; Gene Copy; Transcription Regulation
Version:
Final published version
Additional Links:
http://www.biomedcentral.com/1471-2407/11/378

Full metadata record

DC FieldValue Language
dc.contributor.authorRadhakrishnan, Vijayababuen
dc.contributor.authorPutnam, Charlesen
dc.contributor.authorQi, Wenqingen
dc.contributor.authorMartinez, Jesseen
dc.date.accessioned2016-05-20T09:04:45Z-
dc.date.available2016-05-20T09:04:45Z-
dc.date.issued2011en
dc.identifier.citationRadhakrishnan et al. BMC Cancer 2011, 11:378 http://www.biomedcentral.com/1471-2407/11/378en
dc.identifier.doi10.1186/1471-2407-11-378en
dc.identifier.urihttp://hdl.handle.net/10150/610345-
dc.description.abstractBACKGROUND:14-3-3 proteins are a family of highly conserved proteins that are involved in a wide range of cellular processes. Recent evidence indicates that some of these proteins have oncogenic activity and that they may promote tumorigenesis. We previously showed that one of the 14-3-3 family members, 14-3-3gamma, is over expressed in human lung cancers and that it can induce transformation of rodent cells in vitro.METHODS:qRTPCR and Western blot analysis were performed to examine 14-3-3gamma expression in non-small cell lung cancers (NSCLC). Gene copy number was analyzed by qPCR. P53 mutations were detected by direct sequencing and also by western blot. CHIP and yeast one hybrid assays were used to detect p53 binding to 14-3-3gamma promoter.RESULTS:Quantitative rtPCR results showed that the expression level of 14-3-3gamma was elevated in the majority of NSCLC that we examined which was also consistent with protein expression. Further analysis of the expression pattern of 14-3-3gamma in lung tumors showed a correlation with p53 mutations suggesting that p53 might suppress 14-3-3 gamma expression. Analysis of the gamma promoter sequence revealed the presence of a p53 consensus binding motif and in vitro assays demonstrated that wild-type p53 bound to this motif when activated by ionizing radiation. Deletion of the p53 binding motif eliminated p53's ability to suppress 14-3-3gamma expression.CONCLUSION:Increased expression of 14-3-3gamma in lung cancer coincides with loss of functional p53. Hence, we propose that 14-3-3gamma's oncogenic activities cooperate with loss of p53 to promote lung tumorigenesis.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.biomedcentral.com/1471-2407/11/378en
dc.rights© 2011 Radhakrishnan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.subjectLung canceren
dc.subject14-3-3en
dc.subjectp53 mutationsen
dc.subjectGene Copyen
dc.subjectTranscription Regulationen
dc.titleP53 suppresses expression of the 14-3-3gamma oncogeneen
dc.typeArticleen
dc.identifier.eissn 1471-2407en
dc.contributor.departmentArizona Cancer Center, Department of Cellular & Molecular Medicine, University of Arizona, Tucson, Arizona 85724, USAen
dc.contributor.departmentDepartment of Pediatrics, Steele Research Center, 1501 N Campbell Ave, Tucson, Arizona 85724, USAen
dc.contributor.departmentDepartment of Surgery, 1501 N Campbell ave, Tucson, Arizona 85724, USAen
dc.contributor.departmentDepartment of Medicine, 1515 N. Campbell Ave., Tucson, Arizona 85724, USAen
dc.identifier.journalBMC Canceren
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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