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

Vijayababu M. Radhakrishnan, Charles W. Putnam, Wenqing Qi, Jesse D Martinez

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Article number378
JournalBMC Cancer
Volume11
DOIs
StatePublished - Aug 25 2011

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Oncogenes
Non-Small Cell Lung Carcinoma
Lung Neoplasms
Carcinogenesis
Western Blotting
14-3-3 Proteins
Lung
Mutation
Proteins
Aptitude
Gene Dosage
Ionizing Radiation
Rodentia
Consensus
Yeasts
Neoplasms
In Vitro Techniques

Keywords

  • 14-3-3
  • Gene copy
  • Lung cancer
  • P53 mutations
  • Transcription regulation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

Cite this

P53 suppresses expression of the 14-3-3gamma oncogene. / Radhakrishnan, Vijayababu M.; Putnam, Charles W.; Qi, Wenqing; Martinez, Jesse D.

In: BMC Cancer, Vol. 11, 378, 25.08.2011.

Research output: Contribution to journalArticle

Radhakrishnan, Vijayababu M. ; Putnam, Charles W. ; Qi, Wenqing ; Martinez, Jesse D. / P53 suppresses expression of the 14-3-3gamma oncogene. In: BMC Cancer. 2011 ; Vol. 11.
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