Transcriptomics

Dataset Information

18

Genomics of signalling crosstalk of estrogen receptor alpha in breast cancer cells


ABSTRACT: 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. We show that estrogen, growth factors and cAMP elicit surprisingly distinct ERa-dependent 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 antiestrogen 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. Thus, 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 ERa-dependent carcinomas. Keywords: treatment response Overall design: 10 treatment conditions (3 biological replicates for each, totalling 30 individual samples), of which 3 were untreated controls. Each replicate was hybridized to a separate chip, totalling 27 cDNA slides representing 9 unique conditions.

INSTRUMENT(S): human 10K E

ORGANISM(S): Homo sapiens  

SUBMITTER: Peter Dudek   

PROVIDER: GSE10466 | GEO | 2008-05-22

SECONDARY ACCESSION(S): PRJNA108025

REPOSITORIES: GEO

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