HOXA5-twist interaction alters p53 homeostasis in breast cancer cells

Ioannis A. Stasinopoulos, Yelena Mironchik, Ana Raman, Flonne Wildes, Paul Winnard, Venu Raman

Research output: Contribution to journalArticle

Abstract

The homeotic gene HOXA5 has been shown to play an important role in breast tumorigenesis. We have shown that loss of p53 correlated with loss of a developmentally regulated transcription factor, HOXA5, in primary breast cancer. Searching for potential protein interacting partners we found that HOXA5 binds to an anti-apoptotic protein, Twist. Furthermore, Twist-overexpressing MCF-7 cells displayed a deregulated p53 response to γ-radiation and decreased regulation of downstream target genes. Using a p53-promoter-reporter system, we demonstrated that HOXA5 could partially restore the inhibitory effects of Twist on p53 target genes. These effects are likely mediated through both the transcriptional up-regulation of p53 and the protein-protein interaction between HOXAS and Twist. Thus, the loss of HOXAS expression could lead to the functional activation of Twist resulting in aberrant cell cycle regulation and promoting breast carcinogenesis.

Original languageEnglish (US)
Pages (from-to)2294-2299
Number of pages6
JournalJournal of Biological Chemistry
Volume280
Issue number3
DOIs
StatePublished - Jan 21 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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