Compromised HOXA5 function can limit p53 expression in human breast tumours

Venu Raman, Shelby A. Martenser, David Reisman, Ella Evron, Wart F. Odenwald, Elizabeth Jaffee, Jeffrey Marks, Saraswati Sukumar

Research output: Contribution to journalArticlepeer-review

Abstract

Expression of the p55 gene protects cells against malignant transformation. Whereas control of p53 degradation has been a subject of intense scrutiny, little is known about the factors that regulate p53 synthesis. Here we show that p53 messenger RNA levels are low in a large proportion of breast tumours. Seeking potential regulators of p53 transcription, we found consensus HOX binding sites in the p53 promoter. Transient transfection of Hox/HOXA5 activated the p53 promoter. Expression of HOXA5 in epithelial cancer cells expressing wild-type p53, but not in isogenic variants lacking the p53 gene, led to apoptotic cell death. Moreover, breast cancer cell lines and patient tumours display a coordinate loss of p53 and HOXA5 mRNA and protein expression. The HOXA5 promoter region was methylated in 16 out of 20 p53-negative breast tumour specimens. We conclude that loss of expression of p53 in human breast cancer may be primarily due to lack of expression of HOXA5.

Original languageEnglish (US)
Pages (from-to)974-978
Number of pages5
JournalNature
Volume405
Issue number6789
DOIs
StatePublished - Jun 22 2000

ASJC Scopus subject areas

  • General

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