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Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
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Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells

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Estrogen regulates JNK1 genomic localization to control gene expression and cell growth in breast cancer cells

Miao Sun1, Gary D Isaacs, Nasun Hah

  • 1Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8511, USA.

Molecular Endocrinology (Baltimore, Md.)
|March 27, 2012
PubMed

Insights

Estrogen and c-Jun N-terminal kinase 1 (JNK1) signaling pathways converge at the genome in breast cancer cells. This interaction, regulated by estrogen receptor alpha (ERα), influences gene expression and cell growth, impacting cancer progression.

Area of Science:

  • Molecular Biology
  • Genomics
  • Cancer Biology

Background:

  • Steroid hormone and MAPK signaling pathways are known to intersect.
  • The precise molecular mechanisms underlying this cross-talk, particularly between estrogen and JNK1, remain largely undefined.

Purpose of the Study:

  • To elucidate the genomic convergence of estrogen receptor alpha (ERα) and c-Jun N-terminal kinase 1 (JNK1) signaling pathways in breast cancer cells.
  • To investigate the functional consequences of this ERα-JNK1 interplay on gene expression and cell proliferation.

Main Methods:

  • Genome-wide analysis of JNK1 binding sites in breast cancer cells.
  • Chromatin immunoprecipitation (ChIP) assays to determine ERα and JNK1 occupancy at target promoters.
  • Kinase activity assays for JNK1.
  • Analysis of gene expression profiles and breast cancer patient data.

Main Results:

  • JNK1 binds to numerous genomic promoters, with a subset being estrogen-regulated.
  • ERα is essential for JNK1 recruitment to specific DNA elements, often involving activating protein-1.
  • JNK1 acts as a kinase-dependent transcriptional coregulator of ERα at target promoters.
  • This convergence regulates estrogen-dependent gene expression and cell growth.

Conclusions:

  • Estrogen and JNK1 signaling pathways functionally converge at the genomic level in breast cancer.
  • The interplay between ERα and JNK1 influences estrogen-driven gene expression and cell proliferation.
  • This ERα-JNK1 functional interplay may play a significant role in breast cancer progression and clinical outcomes.

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