Transcriptional factors p300 and MRTF-A synergistically enhance the expression of migration-related genes in MCF-7 breast cancer cells

Biochem Biophys Res Commun. 2015 Nov 27;467(4):813-20. doi: 10.1016/j.bbrc.2015.10.060. Epub 2015 Oct 19.

Abstract

The transcriptional coactivator p300 is highly expressed in breast cancer tissues. MRTF-A is a transcription factor governed by the Rho-GTPase-actin signaling pathway. The purpose of this study was to explore the role of p300 in breast cancer metastasis. Here we showed that the motility of breast cancer cells was enhanced by the overexpression of p300, meanwhile, the transcription of migration-related genes was upregulated. Depletion of p300 downregulated the migration-related genes and slowed down the migration of breast cancer cells. p300 worked synergistically with MRTF-A to activate the transcription of MYH9, MYL9 and CYR61. As identified by co-IP, p300 interacted with the C-terminal TAD domain of MRTF-A. And together with MRTF-A, p300 was associated with the target gene promoters. Furthermore, MRTF-A was found to be acetylated in MCF-7 breast cancer cells. These results demonstrated the involvement of p300 in the MRTF-A mediated gene regulation and breast cancer cell migration.

Keywords: Breast cancer; Cell migration; MRTF-A; Transcription; p300.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • E1A-Associated p300 Protein / genetics
  • E1A-Associated p300 Protein / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MCF-7 Cells
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*

Substances

  • MRTFA protein, human
  • Trans-Activators
  • E1A-Associated p300 Protein
  • EP300 protein, human