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Compromised HOXA5 function can limit p53 expression in human breast tumours.

Publication ,  Journal Article
Raman, V; Martensen, SA; Reisman, D; Evron, E; Odenwald, WF; Jaffee, E; Marks, J; Sukumar, S
Published in: Nature
June 22, 2000

Expression of the p53 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 promoterS. 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.

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Published In

Nature

DOI

ISSN

0028-0836

Publication Date

June 22, 2000

Volume

405

Issue

6789

Start / End Page

974 / 978

Location

England

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Tumor Cells, Cultured
  • Transcription Factors
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Phosphoproteins
  • Mice
  • Humans
  • Homeodomain Proteins
  • Genes, p53
 

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Raman, V., Martensen, S. A., Reisman, D., Evron, E., Odenwald, W. F., Jaffee, E., … Sukumar, S. (2000). Compromised HOXA5 function can limit p53 expression in human breast tumours. Nature, 405(6789), 974–978. https://doi.org/10.1038/35016125
Raman, V., S. A. Martensen, D. Reisman, E. Evron, W. F. Odenwald, E. Jaffee, J. Marks, and S. Sukumar. “Compromised HOXA5 function can limit p53 expression in human breast tumours.Nature 405, no. 6789 (June 22, 2000): 974–78. https://doi.org/10.1038/35016125.
Raman V, Martensen SA, Reisman D, Evron E, Odenwald WF, Jaffee E, et al. Compromised HOXA5 function can limit p53 expression in human breast tumours. Nature. 2000 Jun 22;405(6789):974–8.
Raman, V., et al. “Compromised HOXA5 function can limit p53 expression in human breast tumours.Nature, vol. 405, no. 6789, June 2000, pp. 974–78. Pubmed, doi:10.1038/35016125.
Raman V, Martensen SA, Reisman D, Evron E, Odenwald WF, Jaffee E, Marks J, Sukumar S. Compromised HOXA5 function can limit p53 expression in human breast tumours. Nature. 2000 Jun 22;405(6789):974–978.
Journal cover image

Published In

Nature

DOI

ISSN

0028-0836

Publication Date

June 22, 2000

Volume

405

Issue

6789

Start / End Page

974 / 978

Location

England

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Tumor Cells, Cultured
  • Transcription Factors
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Phosphoproteins
  • Mice
  • Humans
  • Homeodomain Proteins
  • Genes, p53