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p62 overexpression in breast tumors and regulation by prostate-derived Ets factor in breast cancer cells

Oncogene volume 22, pages 2322–2333 (2003)Cite this article

Abstract

p62 is a multifunctional cytoplasmic protein able to noncovalently bind ubiquitin and several signaling proteins, suggesting a regulatory role connected to the ubiquitin–proteasome pathway. No studies to date have linked p62 protein expression with pathological states. Here we demonstrate the overabundance of p62 protein in malignant breast tissue relative to normal breast tissue. The proteasome inhibitor PSI increased p62 mRNA and protein; however, PSI treatment of breast epithelial cells transfected with the p62 promoter did not affect promoter activity. High levels of prostate-derived Ets factor (PDEF) mRNA have been identified in breast cancer compared to normal breast. Only the PSA and maspin promoters have been identified as targets of this transcription factor. Here we show that PDEF stimulates the p62 promoter through at least two sites, and likely acts as a coactivator. PSI treatment abrogates the PDEF-stimulated increase of p62 promoter activity by 50%. Thus, multiple mechanisms for the induction of p62 exist. We conclude that (1) p62 protein is overexpressed in breast cancer; (2) p62 mRNA and protein increase in response to PSI, with no change of basal promoter activity; (3) PDEF upregulates p62 promoter activity through at least two sites; and (4) PSI downregulates PDEF-induced p62 promoter activation through one of these sites.

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Acknowledgements

Some tissue samples were provided by the Cooperative Human Tissue Network, which is funded by the National Cancer Institute. This work was supported by the National Institutes of Health Human Genome Research Institute Grant number 1K22HG00047-01.

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Authors and Affiliations

  1. Department of Biomedical Engineering, University of California, Irvine 204 Rockwell Engineering Center, Irvine, 92697-2715, CA, USA

    H Garrett R Thompson, Joseph W Harris & James P Brody

  2. Department of Biology, California Institute of Technology, 1200 E. California Blvd., Pasadena, 91125, CA, USA

    Barbara J Wold

  3. Irvine Medical Center, University of California, 101 The City Drive South Orange, 92868, CA, USA

    Fritz Lin

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Correspondence to James P Brody.

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Thompson, H., Harris, J., Wold, B. et al. p62 overexpression in breast tumors and regulation by prostate-derived Ets factor in breast cancer cells. Oncogene 22, 2322–2333 (2003). https://doi.org/10.1038/sj.onc.1206325

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