ArticleBreast cancer research : BCR2009
Ku proteins interact with activator protein-2 transcription factors and contribute to ERBB2 overexpression in breast cancer cell lines.
Article in Breast cancer research : BCR, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Interaction of TFAP2A with the Ku70/80 complex is crucial for HIF-dependent activation of hypoxia-inducible genes.The FEBS journal · 2025Article
- Upregulated Expression of ERBB2/HER2 in Multiple Myeloma as a Predictor of Poor Survival Outcomes.International journal of molecular sciences · 2023Article
- Crucial role of the transcription factors family activator protein 2 in cancer: current clue and views.Journal of translational medicine · 2023Review
- Review
- DCLK1 promotes colorectal cancer stemness and aggressiveness via the XRCC5/COX2 axis.Theranostics · 2022Article
- TRIM37 Augments AP-2γ Transcriptional Activity and Cellular Localization via K63-linked Ubiquitination to Drive Breast Cancer Progression.International journal of biological sciences · 2022Article
- Differential expression and transcription factor binding associated with genotype at a pharmacogenetic variant inThe American journal of drug and alcohol abuse · 2021Article
- The Ku complex: recent advances and emerging roles outside of non-homologous end-joining.Cellular and molecular life sciences : CMLS · 2021Review
- AMolecular cancer research : MCR · 2020Article
- Integrated analysis of transcription factors and targets co-expression profiles reveals reduced correlation between transcription factors and target genes in cancer.Functional & integrative genomics · 2019Article
- Chromatin association of XRCC5/6 in the absence of DNA damage depends on the XPE gene product DDB2.Molecular biology of the cell · 2017Article
- The HER2 Signaling Network in Breast Cancer--Like a Spider in its Web.Journal of mammary gland biology and neoplasia · 2014Review
- Transcriptional regulation prediction of antiestrogen resistance in breast cancer based on RNA polymerase II binding data.BMC bioinformatics · 2014Article
- Ku70 functions in addition to nonhomologous end joining in pancreatic β-cells: a connection to β-catenin regulation.Diabetes · 2013Article
- Targeting abnormal DNA repair in therapy-resistant breast cancers.Molecular cancer research : MCR · 2012Article
- Oxidative DNA damage in neurons: implication of ku in neuronal homeostasis and survival.International journal of cell biology · 2012Article
- Mismatch-repair protein MSH6 is associated with Ku70 and regulates DNA double-strand break repair.Nucleic acids research · 2011Article
- The DNA repair complex Ku70/86 modulates Apaf1 expression upon DNA damage.Cell death and differentiation · 2011Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionActivator protein-2 (AP-2) alpha and AP-2gamma transcription factors contribute to ERBB2 gene overexpression in breast cancer. In order to understand the mechanism by which the ERBB2 gene is overexpressed we searched for novel AP-2 interacting factors that contribute to its activity.
methodsKu proteins were identified as AP-2alpha interacting proteins by glutathione serine transferase (GST)-pull down followed by mass spectrometry. Transfection of the cells with siRNA, expression vectors and reporter vectors as well as chromatin immunoprecipitation (ChIP) assay were used to ascertain the implication of Ku proteins on ERBB2 expression.
resultsNuclear proteins from BT-474 cells overexpressing AP-2alpha and AP-2gamma were incubated with GST-AP2 or GST coated beads. Among the proteins retained specifically on GST-AP2 coated beads Ku70 and Ku80 proteins were identified by mass spectrometry. The contribution of Ku proteins to ERBB2 gene expression in BT-474 and SKBR3 cell lines was investigated by downregulating Ku proteins through the use of specific siRNAs. Depletion of Ku proteins led to downregulation of ERBB2 mRNA and protein levels. Furthermore, reduction of Ku80 in HCT116 cell line decreased the AP-2alpha activity on a reporter vector containing an AP-2 binding site linked to the ERBB2 core promoter, and transfection of Ku80 increased the activity of AP-2alpha on this promoter. Ku siRNAs also inhibited the activity of this reporter vector in BT-474 and SKBR3 cell lines and the activity of the ERBB2 promoter was further reduced by combining Ku siRNAs with AP-2alpha and AP-2gamma siRNAs. ChIP experiments with chromatin extracted from wild type or AP-2alpha and AP-2gamma or Ku70 siRNA transfected BT-474 cells demonstrated Ku70 recruitment to the ERBB2 proximal promoter in association with AP-2alpha and AP-2gamma. Moreover, Ku70 siRNA like AP-2 siRNAs, greatly reduced PolII recruitment to the ERBB2 proximal promoter.
conclusionsKu proteins in interaction with AP-2 (alpha and gamma) contribute to increased ERBB2 mRNA and protein levels in breast cancer cells.
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