UNIGE document Scientific Article
previous document  unige:13247  next document
add to browser collection
Title

Genomics of Signaling Crosstalk of Estrogen Receptor α in Breast Cancer Cells

Authors
Dudeck, Peter
Published in PLOS ONE. 2009, vol. 3, no. 3
Abstract Background: The estrogen receptor a (ERa) is a ligand-regulated transcription factor. However, a wide variety of other extracellular signals can activate ERa in the absence of estrogen. The impact of these alternate modes of activation on gene expression profiles has not been characterized. Methodology/Principal Findings: We show that estrogen, growth factors and cAMP elicit surprisingly distinct ERadependent transcriptional responses in human MCF7 breast cancer cells. In response to growth factors and cAMP, ERa primarily activates and represses genes, respectively. The combined treatments with the anti-estrogen tamoxifen and cAMP or growth factors regulate yet other sets of genes. In many cases, tamoxifen is perverted to an agonist, potentially mimicking what is happening in certain tamoxifen-resistant breast tumors and emphasizing the importance of the cellular signaling environment. Using a computational analysis, we predicted that a Hox protein might be involved in mediating such combinatorial effects, and then confirmed it experimentally. Although both tamoxifen and cAMP block the proliferation of MCF7 cells, their combined application stimulates it, and this can be blocked with a dominant-negative Hox mutant. Conclusions/Significance: The activating signal dictates both target gene selection and regulation by ERa, and this has consequences on global gene expression patterns that may be relevant to understanding the progression of ERadependent carcinomas.
Stable URL http://archive-ouverte.unige.ch/unige:13247
Full text
Article (Published version) (535 Kb) - public document Free access
Identifiers
PMID: 18365014
Structures

118 hits

60 downloads

Update

Deposited on : 2011-01-24

Export document
Format :
Citation style :