PKA-Mediated stabilization of FoxH1 negatively regulates ERα activity

Jinah Yum, Hyung Min Jeong, Seulki Kim, Jin Won Seo, Younho Han, Kwang Youl Lee, Chang Yeol Yeo

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Estrogen receptor α (ERα) mediates the mitogenic effects of estrogen. ERα signaling regulates the normal growth and differentiation of mammary tissue, but uncontrolled ERα activation increases the risk to breast cancer. Estrogen binding induces ligand-dependent ERα activation, thereby facilitating ERα dimerization, promoter binding and coactivator recruitment. ERα can also be activated in a ligand-independent manner by many signaling pathways, including protein kinase A (PKA) signaling. However, in several ERα-positive breast cancer cells, PKA inhibits estrogen-dependent cell growth. FoxH1 represses the transcriptional activities of estrogen receptors and androgen receptors (AR). Interestingly, FoxH1 has been found to inhibit the PKA-induced and ligand-induced activation of AR. In the present study, we examined the effects of PKA activation on the ability of FoxH1 to represses ERα transcriptional activity. We found that PKA increases the protein stability of FoxH1, and that FoxH1 inhibits PKA-induced and estradiol-induced activation of an estrogen response element (ERE). Furthermore, in MCF7 cells, FoxH1 knockdown increased the PKA-induced and estradiol-induced activation of the ERE. These results suggest that PKA can negatively regulate ERα, at least in part, through FoxH1.

Original languageEnglish
Pages (from-to)67-71
Number of pages5
JournalMolecules and Cells
Volume28
Issue number1
DOIs
StatePublished - 2009

Bibliographical note

Funding Information:
This work was supported by a Korea Research Foundation Grant funded by the Korean Government (Ministry of Education and Human Resources Development, Basic Research Promotion Fund) (KRF-2006-312-C00350) to C.-Y. Yeo. J. Yum and S. Kim were supported by the second stage of the Brain Korea 21 P roject.

Keywords

  • Estrogen receptor α
  • FoxH1
  • Protein kinase A
  • Protein stability

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