Transcriptional repression of the human collagenase-1 (MMP-1) gene in MDA231 breast cancer cells by all-trans-retinoic acid requires distal regions of the promoter
1999

How Retinoic Acid Affects Collagenase-1 in Breast Cancer Cells

publication

Author Information

Author(s): Benbow U, Rutter J L, Lowrey C H, Brinckerhoff C E

Primary Institution: Dartmouth Medical School

Hypothesis

The study investigates how all-trans-retinoic acid regulates the transcription of the collagenase-1 gene in breast cancer cells.

Conclusion

Collagenase-1 repression in MDA231 cells occurs through a novel regulatory pathway that relies on distal promoter regions rather than the proximal AP-1 site.

Supporting Evidence

  • The study implicates several PEA3 sites in the expression of the collagenase-1 promoter.
  • Repression of collagenase-1 transcription by retinoic acid does not depend on the proximal AP-1 site.
  • The PEA3 site at -3108 bp is suggested to facilitate transcriptional repression.

Takeaway

This study shows that a substance called retinoic acid can turn off a gene important for cancer cell invasion, but it does so by using parts of the gene's control region that are far away from the gene itself.

Methodology

The study used in vivo and in vitro experiments, including DNAase I hypersensitivity assays, transient transfection of promoter constructs, and electrophoretic mobility shift assays.

Digital Object Identifier (DOI)

10.1038/sj.bjc.6690037

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication