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The SLUG zinc-finger protein represses E-cadherin in breast cancer.

Loss of expression of the E-cadherin cell-cell adhesion molecule is important in carcinoma development and progression. Because previous data suggest that loss of E-cadherin expression in breast carcinoma may result from a dominant transcriptional repression pathway acting on the E-cadherin proximal promoter, we pursued studies of cis sequences and transcription factors regulating E-cadherin expression in breast cancer cells. E-box elements in the E-cadherin promoter were found to play a critical negative regulatory role in E-cadherin gene transcription in breast cancer cell lines lacking E-cadherin transcription. The E-box elements had a minimal role in E-cadherin transcription in breast cancer cell lines expressing E-cadherin. Two zinc-finger transcription factors known to bind E-box elements, SLUG and SNAIL, repressed E-cadherin-driven reporter gene constructs containing wild-type promoter sequences but not those with mutations in the E-box elements. Additionally, both SLUG and SNAIL repressed endogenous E-cadherin expression. These findings suggest SLUG and SNAIL are potential repressors of E-cadherin transcription in carcinomas lacking E-cadherin expression. Analysis of the expression patterns of SLUG, SNAIL, and E-cadherin in breast cancer cell lines demonstrated that expression of SLUG was strongly correlated with loss of E-cadherin transcripts. Taken together, the data indicate the E-box elements in the proximal E-cadherin promoter are critical in transcriptional repression of the E-cadherin gene, and SLUG is a likely in vivo repressor of E-cadherin in breast cancer.

Pubmed ID: 11912130

Authors

  • Hajra KM
  • Chen DY
  • Fearon ER

Journal

Cancer research

Publication Data

March 15, 2002

Associated Grants

  • Agency: NCI NIH HHS, Id: T32 CA09676

Mesh Terms

  • Breast Neoplasms
  • Cadherins
  • DNA-Binding Proteins
  • E-Box Elements
  • Humans
  • Promoter Regions, Genetic
  • Repressor Proteins
  • Transcription Factors
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Zinc Fingers