scholarly journals Integration of Estrogen and Wnt Signaling Circuits by the Polycomb Group Protein EZH2 in Breast Cancer Cells

2007 ◽  
Vol 27 (14) ◽  
pp. 5105-5119 ◽  
Author(s):  
Bin Shi ◽  
Jing Liang ◽  
Xiaohan Yang ◽  
Yan Wang ◽  
Youna Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Transcriptional Activation ◽  
Breast Cancer Cells ◽  
Polycomb Group ◽  
Dual Function ◽  
Polycomb Group Protein ◽  
Dynamic Activity ◽  
Group Protein

ABSTRACT Essential for embryonic development, the polycomb group protein enhancer of zeste homolog 2 (EZH2) is overexpressed in breast and prostate cancers and is implicated in the growth and aggression of the tumors. The tumorigenic mechanism underlying EZH2 overexpression is largely unknown. It is believed that EZH2 exerts its biological activity as a transcription repressor. However, we report here that EZH2 functions in gene transcriptional activation in breast cancer cells. We show that EZH2 transactivates genes that are commonly targeted by estrogen and Wnt signaling pathways. We demonstrated that EZH2 physically interacts directly with estrogen receptor α and β-catenin, thus connecting the estrogen and Wnt signaling circuitries, functionally enhances gene transactivation by estrogen and Wnt pathways, and phenotypically promotes cell cycle progression. In addition, we identified the transactivation activity of EZH2 in its two N-terminal domains and demonstrated that these structures serve as platforms to connect transcription factors and the Mediator complex. Our experiments indicated that EZH2 is a dual function transcription regulator with a dynamic activity, and we provide a mechanism for EZH2 in tumorigenesis.

Evidence for transcriptional activation of ERalpha by IL-1beta in breast cancer cells.

1999 ◽  
Author(s):  
V Speirs ◽  
M J Kerin ◽  
C J Newton ◽  
D S Walton ◽  
A R Green ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Transcriptional Activation ◽  
Breast Cancer Cells

Abstract 57: Twist1 modifies the metabolic state of breast cancer cells through transcriptional activation of a key regulator of glycolysis

2016 ◽  
Author(s):  
Esmeralda Casas ◽  
Antonio F. Santidrian ◽  
Mihaela Lorger ◽  
Ali Torkamani ◽  
Boris Ratnikov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Transcriptional Activation ◽  
Breast Cancer Cells ◽  
Metabolic State

TMEPAI/PMEPA1 inhibits Wnt signaling by regulating β-catenin stability and nuclear accumulation in triple negative breast cancer cells

2019 ◽  
Vol 59 ◽  
pp. 24-33 ◽  
Author(s):  
Riezki Amalia ◽  
Mohammed Abdelaziz ◽  
Meidi Utami Puteri ◽  
Jongchan Hwang ◽  
Femmi Anwar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Nuclear Accumulation

scholarly journals Acquisition of a hybrid E/M state is essential for tumorigenicity of basal breast cancer cells

2019 ◽  
Vol 116 (15) ◽  
pp. 7353-7362 ◽  
Author(s):  
Cornelia Kröger ◽  
Alexander Afeyan ◽  
Jasmin Mraz ◽  
Elinor Ng Eaton ◽  
Ferenc Reinhardt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Ectopic Expression ◽  
Hybrid State ◽  
Marker Combination ◽  
Basal Breast Cancer ◽  
Phenotypic State

Carcinoma cells residing in an intermediate phenotypic state along the epithelial–mesenchymal (E–M) spectrum are associated with malignant phenotypes, such as invasiveness, tumor-initiating ability, and metastatic dissemination. Using the recently described CD104+/CD44hi antigen marker combination, we isolated highly tumorigenic breast cancer cells residing stably—both in vitro and in vivo—in an intermediate phenotypic state and coexpressing both epithelial (E) and mesenchymal (M) markers. We demonstrate that tumorigenicity depends on individual cells residing in this E/M hybrid state and cannot be phenocopied by mixing two cell populations that reside stably at the two ends of the spectrum, i.e., in the E and in the M state. Hence, residence in a specific intermediate state along the E–M spectrum rather than phenotypic plasticity appears critical to the expression of tumor-initiating capacity. Acquisition of this E/M hybrid state is facilitated by the differential expression of EMT-inducing transcription factors (EMT-TFs) and is accompanied by the expression of adult stem cell programs, notably, active canonical Wnt signaling. Furthermore, transition from the highly tumorigenic E/M state to a fully mesenchymal phenotype, achieved by constitutive ectopic expression of Zeb1, is sufficient to drive cells out of the E/M hybrid state into a highly mesenchymal state, which is accompanied by a substantial loss of tumorigenicity and a switch from canonical to noncanonical Wnt signaling. Identifying the gatekeepers of the various phenotypic states arrayed along the E–M spectrum is likely to prove useful in developing therapeutic approaches that operate by shifting cancer cells between distinct states along this spectrum.

scholarly journals Induction of multidrug resistance associated protein 2 in tamoxifen-resistant breast cancer cells

2007 ◽  
Vol 14 (2) ◽  
pp. 293-303 ◽  
Author(s):  
Hoo Kyun Choi ◽  
Jin Won Yang ◽  
Sang Hee Roh ◽  
Chang Yeob Han ◽  
Keon Wook Kang
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Transcriptional Activation ◽  
Breast Cancer Cells ◽  
Pregnane X Receptor ◽  
Pi3 Kinase ◽  
Gene Promoters ◽  
Breast Cancer Patients ◽  
Mcf 7

Acquired resistance to tamoxifen (TAM) is a serious therapeutic problem in breast cancer patients. The transition from chemotherapy-responsive breast cancer cells to chemotherapy-resistant cancer cells is mainly accompanied by the increased expression of multidrug resistance-associated proteins (MRPs). In this study, it was found that TAM-resistant MCF-7 (TAMR-MCF-7) cells expressed higher levels of MRP2 than control MCF-7 cells. Molecular analyses using MRP2 gene promoters supported the involvement of the pregnane X receptor (PXR) in MRP2 overexpression in TAMR-MCF-7 cells. Although CCAAT/enhancer-binding protein β was overexpressed continuously in TAMR-MCF-7 cells, this might not be responsible for the transcriptional activation of the MRP2 gene. In addition, the basal activities of phosphatidylinositol 3-kinase (PI3-kinase) were higher in the TAMR-MCF-7 cells than in the control cells. The inhibition of PI3-kinase significantly reduced both the PXR activity and MRP2 expression in TAMR-MCF-7 cells. Overall, MRP2 induction plays a role in the additional acquisition of chemotherapy resistance in TAM-resistant breast cancer.

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