Transcriptomics

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The anti-proliferative effects of progestins in T47D breast cancer cells are tempered by progestin-induction of the ETS transcription factor Elf5.


ABSTRACT: Prolactin and progesterone act together to regulate mammary alveolar development, and both hormones have been implicated in breast cancer initiation and progression. Here we show that Elf5, a prolactin-induced ETS transcription factor that specifies the mammary secretory cell lineage, is also induced by progestins in breast cancer cells via a direct mechanism. To define the transcriptional response to progestin elicited via Elf5 we made an inducible Elf5 sh-RNA knock down model in T47D breast cancer cells and used it to prevent the progestin-induction of Elf5. Functional analysis of Affymetrix gene expression data using Gene Ontologies and Gene Set Enrichment Analysis showed enhancement of the progestin effects on cell cycle gene expression. Cell proliferation assays showed a more efficacious progestin-induced growth arrest when Elf5 was kept at baseline levels. These results showed that progestin-induction of Elf5 expression tempered the anti-proliferative effects of progestins in T47D cells, providing a further mechanistic link between prolactin and progestin in the regulation of mammary cell phenotype. We used Affymetrix expression arrays to determine to what extent Elf5 mediated the transcriptional effects of progestins in T47D cells. We transcript profiled our inducible Elf5 hold-down model using triplicate independent experiments under three conditions: (1) treatment with ethanol vehicle only (Baseline), (2) ORG2058 treatment for 4 days (Pg), and (3) Dox and ORG2058 treatment for 4 days, (Pg-Elf5) designed to prevent the progestin-induction of Elf5 expression.

ORGANISM(S): Homo sapiens  

SUBMITTER: Maria Kalyuga   Heidi N Hilton   Christine L Clarke  Justine D Graham  Mark J Cowley  Mark Cowley  Catherine E Caldon  Elizabeth A Musgrove  Marie C Alles  Katrina Blazek  Christopher J Ormandy  Matt J Naylor  Heather J Lee  Roger J Daly  Warren Kaplan 

PROVIDER: E-GEOD-22363 | ArrayExpress | 2010-07-08

SECONDARY ACCESSION(S): GSE22363PRJNA127673

REPOSITORIES: GEO, ArrayExpress

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