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Compromised HOXA5 function can limit p53 expression in human breast tumours

Author

Listed:
  • Venu Raman

    (Breast Cancer Program, Johns Hopkins Oncology Center)

  • Shelby A. Martensen

    (Breast Cancer Program, Johns Hopkins Oncology Center)

  • David Reisman

    (University of South Carolina)

  • Ella Evron

    (Breast Cancer Program, Johns Hopkins Oncology Center)

  • Ward F. Odenwald

    (National Institutes of Health)

  • Elizabeth Jaffee

    (Breast Cancer Program, Johns Hopkins Oncology Center)

  • Jeffrey Marks

    (Duke University Medical Center)

  • Saraswati Sukumar

    (Breast Cancer Program, Johns Hopkins Oncology Center)

Abstract

Expression of the p53 gene protects cells against malignant transformation1,2. Whereas control of p53 degradation has been a subject of intense scrutiny, little is known about the factors that regulate p53 synthesis1,2. 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 sites3,4 in the p53 promoter5. 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 gene6, 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.

Suggested Citation

  • Venu Raman & Shelby A. Martensen & David Reisman & Ella Evron & Ward F. Odenwald & Elizabeth Jaffee & Jeffrey Marks & Saraswati Sukumar, 2000. "Compromised HOXA5 function can limit p53 expression in human breast tumours," Nature, Nature, vol. 405(6789), pages 974-978, June.
    • Handle: RePEc:nat:nature:v:405:y:2000:i:6789:d:10.1038_35016125
    DOI: 10.1038/35016125
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