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Publication : HOXA5-twist interaction alters p53 homeostasis in breast cancer cells.

First Author  Stasinopoulos IA Year  2005
Journal  J Biol Chem Volume  280
Issue  3 Pages  2294-9
PubMed ID  15545268 Mgi Jnum  J:96147
Mgi Id  MGI:3529613 Doi  10.1074/jbc.M411018200
Citation  Stasinopoulos IA, et al. (2005) HOXA5-twist interaction alters p53 homeostasis in breast cancer cells. J Biol Chem 280(3):2294-9
abstractText  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 gamma-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 HOXA5 and Twist. Thus, the loss of HOXA5 expression could lead to the functional activation of Twist resulting in aberrant cell cycle regulation and promoting breast carcinogenesis.
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