ArticleMolecular cancer2010
BEX2 has a functional interplay with c-Jun/JNK and p65/RelA in breast cancer.
Article in Molecular cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Biological potential and mechanisms of Brain-Expressed X-linked family proteins in cancers: an updated review.Journal of advanced research · 2026Review
- BEX2 regulates autophagy by inhibiting PIK3CA-p85 interaction in non-small-cell lung cancer cells.Cell communication and signaling : CCS · 2025Article
- Article
- FUS-ALS hiPSC-derived astrocytes impair human motor units through both gain-of-toxicity and loss-of-support mechanisms.Molecular neurodegeneration · 2023Article
- Comprehensive Analysis of the Brain-Expressed X-Link Protein Family in Glioblastoma Multiforme.Frontiers in oncology · 2022Article
- BEX2 is required for maintaining dormant cancer stem cell in hepatocellular carcinoma.Cancer science · 2021Article
- Divalent Metal Transporter 1 Knock-Down Modulates IL-1β Mediated Pancreatic Beta-Cell Pro-Apoptotic Signaling Pathways through the Autophagic Machinery.International journal of molecular sciences · 2021Article
- BEX2 suppresses mitochondrial activity and is required for dormant cancer stem cell maintenance in intrahepatic cholangiocarcinoma.Scientific reports · 2020Article
- Silencing of brain-expressed X-linked 2 (BEX2) promotes colorectal cancer metastasis through the Hedgehog signaling pathway.International journal of biological sciences · 2020Article
- C1orf64 is a novel androgen receptor target gene and coregulator that interacts with 14-3-3 protein in breast cancer.Oncotarget · 2017Article
- BEX2 promotes tumor proliferation in colorectal cancer.International journal of biological sciences · 2017Article
- Oncogenic microtubule hyperacetylation through BEX4-mediated sirtuin 2 inhibition.Cell death & disease · 2016Article
- Brain-expressed X-linked 2 Is Pivotal for Hyperactive Mechanistic Target of Rapamycin (mTOR)-mediated Tumorigenesis.The Journal of biological chemistry · 2015Article
- Notch-mediated expansion of cord blood progenitors: maintenance of transcriptional and epigenetic fidelity.Leukemia · 2015Article
- Brain expressed and X-linked (Bex) proteins are intrinsically disordered proteins (IDPs) and form new signaling hubs.PloS one · 2015Article
- Bex2 controls proliferation of human glioblastoma cells through NF-κB signaling pathway.Journal of molecular neuroscience : MN · 2014Article
- Article
- Bex2 is critical for migration and invasion in malignant glioma cells.Journal of molecular neuroscience : MN · 2013Article
- Interleukin-1β enhances cell migration through AP-1 and NF-κB pathway-dependent FGF2 expression in human corneal endothelial cells.Biology of the cell · 2013Article
- Prolactin-induced protein mediates cell invasion and regulates integrin signaling in estrogen receptor-negative breast cancer.Breast cancer research : BCR · 2012Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe have previously demonstrated that BEX2 is differentially expressed in breast tumors and has a significant role in promoting cell survival and growth in breast cancer cells. BEX2 expression protects breast cancer cells against mitochondrial apoptosis and G1 cell cycle arrest. In this study we investigated the transcriptional regulation of BEX2 and feedback mechanisms mediating the cellular function of this gene in breast cancer.
resultsWe found a marked induction of BEX2 promoter by c-Jun and p65/RelA using luciferase reporter assays in MCF-7 cells. Furthermore, we confirmed the binding of c-Jun and p65/RelA to the BEX2 promoter using a chromatin immunoprecipitation assay. Importantly, transfections of c-Jun or p65/RelA in MCF-7 cells markedly increased the expression of BEX2 protein. Overall, these results demonstrate that BEX2 is a target gene for c-Jun and p65/RelA in breast cancer. These findings were further supported by the presence of a strong correlation between BEX2 and c-Jun expression levels in primary breast tumors. Next we demonstrated that BEX2 has a feedback mechanism with c-Jun and p65/RelA in breast cancer. In this process BEX2 expression is required for the normal phosphorylation of p65 and IkappaB alpha, and the activation of p65. Moreover, it is necessary for the phosphorylation of c-Jun and JNK kinase activity in breast cancer cells. Furthermore, using c-Jun stable lines we showed that BEX2 expression is required for c-Jun mediated induction of cyclin D1 and cell proliferation. Importantly, BEX2 down-regulation resulted in a significant increase in PP2A activity in c-Jun stable lines providing a possible underlying mechanism for the regulatory effects of BEX2 on c-Jun and JNK.
conclusionsThis study shows that BEX2 has a functional interplay with c-Jun and p65/RelA in breast cancer. In this process BEX2 is a target gene for c-Jun and p65/RelA and in turn regulates the phosphorylation/activity of these proteins. These suggest that BEX2 is involved in a novel feedback mechanism with significant implications for the biology of breast cancer.
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