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A role for candidate tumor-suppressor gene TCEAL7 in the regulation of c-Myc activity, cyclin D1 levels and cellular transformation

Oncogene volume 27, pages 7223–7234 (2008)Cite this article

Abstract

The pathophysiological mechanisms that drive the development and progression of epithelial ovarian cancer remain obscure. Recently, we identified TCEAL7 as a transcriptional regulatory protein often downregulated in epithelial ovarian cancer. However, the biological significance of such downregulation in cancer is not currently known. Here, we show that TCEAL7 is downregulated frequently in many human cancers and that in immortalized human ovarian epithelial cells this event promotes anchorage-independent cell growth. Mechanistic investigations revealed that TCEAL7 associates with cyclin D1 promoter containing Myc E-box sequence and transcriptionally represses cyclin D1 expression. Moreover, downregulation of TCEAL7 promotes DNA-binding activity of Myc-Max, and upregulates the promoter activity of c-Myc-target gene, ornithine decarboxylase (ODC), whereas enhanced expression of TCEAL7 inhibits Myc-induced promoter activity of ODC. Our findings suggest that TCEAL7 may restrict ovarian epithelial cell transformation by limiting Myc activity. These results also suggest a potential, alternative mechanism by which c-Myc activity may be deregulated in cancer by the downregulation of TCEAL7.

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Acknowledgements

This study was funded by Fraternal Order of Eagle to VS, by Department of Defense OCRP W81XWH-04-1-0085 to VS, and by Edith and Bernie Waterman Foundation and the Mayo Foundation to VS.

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Authors and Affiliations

  1. Division of Experimental Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA

    J Chien, R Rattan, J Staub, D Beleford & V Shridhar

  2. Department of Anatomy and Cell Biology, University of Yamanashi Faculty of Medicine, 1110 Shimo-Kato, Chuo Yamanashi, Japan

    K Narita

  3. Department of Pediatrics, Children Research Institute, Medical University of South Carolina, Charleston, SC, USA

    S Giri

  4. Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, MI, USA

    R Shridhar

  5. Department of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA

    J Lai & L R Roberts

  6. Department of Medical Oncology, Mayo Clinic College of Medicine, Rochester, MN, USA

    J Molina

  7. Department of Oncology Research, Mayo Clinic College of Medicine, Rochester, MN, USA

    S H Kaufmann

  8. Lankenau Institute for Medical Research, Wynnewood, PA, USA

    G C Prendergast

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  1. J Chien
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Correspondence to V Shridhar.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Chien, J., Narita, K., Rattan, R. et al. A role for candidate tumor-suppressor gene TCEAL7 in the regulation of c-Myc activity, cyclin D1 levels and cellular transformation. Oncogene 27, 7223–7234 (2008). https://doi.org/10.1038/onc.2008.360

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