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

J. Chien, K. Narita, R. Rattan, S. Giri, R. Shridhar, J. Staub, D. Beleford, J. Lai, L. R. Roberts, J. Molina, S. H. Kaufmann, G. C. Prendergast, V. Shridhar

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7223-7234
Number of pages12
JournalOncogene
Volume27
Issue number58
DOIs
StatePublished - Dec 11 2008

Keywords

  • Cyclin D1
  • Myc
  • TCEAL7
  • Transformation
  • Tumor suppressor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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