Limiting p53 Expression

Abstract

Inactivation or loss of the tumor suppressor protein p53 results in cell transformation. Raman et al. examine the mechanism by which a decrease in p53 synthesis can also cause tumorigenesis. In a substantial fraction of human breast tumors tested, decrease in p53 mRNA correlated with a decrease in mRNA encoding the HOXA5 transcription factor. HOXA5 was shown to bind directly to the p53 promoter and to activate expression. Expression of HOXA5 in breast cancer cell lines that have the wild-type p53 gene resulted in apoptosis. The authors propose that HOXA5 is a positive regulator of p53 expression. A decrease in HOXA5 expression, possibly due to methylation of the HOXA5 promoter, may therefore account for the reduction in p53 observed in many breast tumors.Raman, V., Martensen, S.A., Reisman, D., Evron, E., Odenwald, W.F., Jaffee, E., Marks, J., and Sukumar, S. (2000) Compromised HOXA5 function can limit p53 expression in human breast tumours. Nature 405:974-978. [Online Journal]