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Open Access Highly Accessed Research article

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

Vijayababu M Radhakrishnan12, Charles W Putnam13, Wenqing Qi14 and Jesse D Martinez1*

Author Affiliations

1 Arizona Cancer Center, Department of Cellular & Molecular Medicine, University of Arizona, Tucson, Arizona 85724, USA

2 Department of Pediatrics, Steele Research Center, 1501 N Campbell Ave, Tucson, Arizona 85724, USA

3 Department of Surgery, 1501 N Campbell ave, Tucson, Arizona 85724, USA

4 Department of Medicine, 1515 N. Campbell Ave., Tucson, Arizona 85724, USA

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BMC Cancer 2011, 11:378  doi:10.1186/1471-2407-11-378

Published: 25 August 2011

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.

Keywords:
Lung cancer; 14-3-3; p53 mutations; Gene Copy; Transcription Regulation