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| Status |
Public on Jun 30, 2014 |
| Title |
Insights into the invasiveness of triple negative breast cancer from genome-wide profiling of transcription factor AP-1 (expression) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Triple negative breast cancer (TNBC) is an aggressive clinical phenotype, and accounts for 15% to 20% of all breast cancers. The molecular determinants of malignant cell behaviors in TNBC remain largely unknown. We find that the AP-1 transcription factor component, Fra-1, is overexpressed in basal-like breast tumors, and its expression level has high prognostic significance. Depletion of Fra-1 or its heterodimeric partner c-Jun inhibits the proliferative and invasive phenotypes in TNBC cells. To gain insights into the transcriptional regulatory networks of AP-1 in TNBC cells, we combine genome-wide ChIP-seq with loss-of-function transcriptome analyses. We observe dysregulation of direct targets of the Fra-1/c-Jun heterodimer involved in cell proliferation, cell adhesion, and cell-cell contact. Intriguingly, we find that AP-1 mediates downregulation of E-cadherin through direct transcriptional induction of ZEB2. This work sheds light on the mechanisms and pathways by which TNBC acquires invasiveness and proliferative propensity.
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| Overall design |
BT549 cells grown in complete medium were transfected with a control siRNA, siRNA targeting Fra-1 or siRNA targeting c-Jun for 72 h, and then global gene expression profiles were assessed. Three or four biological replicates were used for each group.
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| Contributor(s) |
Qiao Y, Dahlman-Wright K, Jonsson P, Williams C, Xu L, Zhao C, Sinha I |
| Citation(s) |
24830720 |
| Submission date |
Apr 26, 2013 |
| Last update date |
Nov 08, 2016 |
| Contact name |
Chunyan Zhao |
| E-mail(s) |
chunyan.zhao@ki.se
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| Phone |
46-8-52481126
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| Fax |
46-8-7745538
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| Organization name |
Karolinska Institute
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| Department |
Biosciences and Nutrition
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| Street address |
Hälsovägen 7-9
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| City |
Stockholm |
| ZIP/Postal code |
SE-171 77 |
| Country |
Sweden |
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| Platforms (1) |
| GPL11532 |
[HuGene-1_1-st] Affymetrix Human Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE46441 |
Insights into the invasiveness of triple negative breast cancer from genome-wide profiling of transcription factor AP-1 |
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| Relations |
| BioProject |
PRJNA200345 |
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