TY - JOUR
T1 - HOXA5-twist interaction alters p53 homeostasis in breast cancer cells
AU - Stasinopoulos, Ioannis A.
AU - Mironchik, Yelena
AU - Raman, Ana
AU - Wildes, Flonne
AU - Winnard, Paul
AU - Raman, Venu
PY - 2005/1/21
Y1 - 2005/1/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=12544249159&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12544249159&partnerID=8YFLogxK
U2 - 10.1074/jbc.M411018200
DO - 10.1074/jbc.M411018200
M3 - Article
C2 - 15545268
AN - SCOPUS:12544249159
VL - 280
SP - 2294
EP - 2299
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 3
ER -