scholarly journals Upregulation of Cyclooxygenase-2/Prostaglandin E2 (COX-2/PGE2) Pathway Member Multiple Drug Resistance-Associated Protein 4 (MRP4) and Downregulation of Prostaglandin Transporter (PGT) and 15-Prostaglandin Dehydrogenase (15-PGDH) in Triple-Negative Breast Cancer

2016 ◽  
Vol 10 ◽  
pp. BCBCR.S38529 ◽  
Author(s):  
Tyler J. Kochel ◽  
Olga G. Goloubeva ◽  
Amy M. Fulton
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Drug Resistance ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Prostaglandin Dehydrogenase ◽  
Cox 2

Elevated levels of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) are indicators of a poor prognosis in breast cancer. Using several independent publicly available breast cancer gene expression databases, we investigated other members of the PGE2 pathway. PGE2 is produced by COX-2 and actively exported by multiple drug resistance-associated protein 4 (MRP4) into the extracellular microenvironment, where PGE2 can bind four cognate EP receptors (EP1–EP4) and initiate diverse biological signaling pathways. Alternatively, PGE2 is imported via the prostaglandin transporter (PGT) and metabolized by 15-prostaglandin dehydrogenase (15-PGDH/HPGD). We made the novel observation that MRP4, PGT, and 15-PGDH are differentially expressed among distinct breast cancer molecular subtypes; this finding was confirmed in independent datasets. In triple-negative breast cancer, the observed gene expression pattern (high COX-2, high MRP4, low PGT, and low 15-PGDH) would favor high levels of tumor-promoting PGE2 in the tumor microenvironment that may contribute to the overall poor prognosis of triple-negative breast cancer.

scholarly journals Bio-Inspired and Smart Nanoparticles for Triple Negative Breast Cancer Microenvironment

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 287
Author(s):  
Mahsa Keihan Shokooh ◽  
Fakhrossadat Emami ◽  
Jee-Heon Jeong ◽  
Simmyung Yook
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Immune Cell ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Her2 Receptor ◽  
Coated Nanoparticles ◽  
Epidermal Growth

Triple negative breast cancer (TNBC) with poor prognosis and aggressive nature accounts for 10–20% of all invasive breast cancer (BC) cases and is detected in as much as 15% of individuals diagnosed with BC. Currently, due to the absence of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) receptor, there is no hormone-based therapy for TNBC. In addition, there are still no FDA-approved targeted therapies for patients with TNBC. TNBC treatment is challenging owing to poor prognosis, tumor heterogeneity, chemotherapeutic side effects, the chance of metastasis, and multiple drug-resistance. Therefore, various bio-inspired tumor-homing nano systems responding to intra- and extra- cellular stimuli are an urgent need to treat TNBC patients who do not respond to current chemotherapy. In this review, intensive efforts have been made for exploring cell-membrane coated nanoparticles and immune cell-targeted nanoparticles (immunotherapy) to modulate the tumor microenvironment and deliver accurate amounts of therapeutic agents to TNBC without stimulating the immune system.

scholarly journals CBP/β-Catenin/FOXM1 Is a Novel Therapeutic Target in Triple Negative Breast Cancer

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 525 ◽  
Author(s):  
Alexander Ring ◽  
Cu Nguyen ◽  
Goar Smbatyan ◽  
Debu Tripathy ◽  
Min Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Drug Resistance ◽  
Triple Negative Breast Cancer ◽  
Therapeutic Target ◽  
Triple Negative ◽  
Creb Binding Protein ◽  
Novel Therapeutic

Background: Triple negative breast cancers (TNBCs) are an aggressive BC subtype, characterized by high rates of drug resistance and a high proportion of cancer stem cells (CSC). CSCs are thought to be responsible for tumor initiation and drug resistance. cAMP-response element-binding (CREB) binding protein (CREBBP or CBP) has been implicated in CSC biology and may provide a novel therapeutic target in TNBC. Methods: RNA Seq pre- and post treatment with the CBP-binding small molecule ICG-001 was used to characterize CBP-driven gene expression in TNBC cells. In vitro and in vivo TNBC models were used to determine the therapeutic effect of CBP inhibition via ICG-001. Tissue microarrays (TMAs) were used to investigate the potential of CBP and associated proteins as biomarkers in TNBC. Results: The CBP/ß-catenin/FOXM1 transcriptional complex drives gene expression in TNBC and is associated with increased CSC numbers, drug resistance and poor survival outcome. Targeting of CBP/β-catenin/FOXM1 with ICG-001 eliminated CSCs and sensitized TNBC tumors to chemotherapy. Immunohistochemistry of TMAs demonstrated a significant correlation between FOXM1 expression and TNBC subtype. Conclusion: CBP/β-catenin/FOXM1 transcriptional activity plays an important role in TNBC drug resistance and CSC phenotype. CBP/β-catenin/FOXM1 provides a molecular target for precision therapy in triple negative breast cancer and could form a rationale for potential clinical trials.

scholarly journals Correction to: New insights in gene expression alteration as effect of doxorubicin drug resistance in triple negative breast cancer cells

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Cristina Alexandra Ciocan-Cartita ◽  
Ancuta Jurj ◽  
Oana Zanoaga ◽  
Roxana Cojocneanu ◽  
Laura-Ancuta Pop ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Gene Expression Alteration

An amendment to this paper has been published and can be accessed via the original article.

scholarly journals New insights in gene expression alteration as effect of doxorubicin drug resistance in triple negative breast cancer cells

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Cristina Alexandra Ciocan-Cartita ◽  
Ancuta Jurj ◽  
Oana Zanoaga ◽  
Roxana Cojocneanu ◽  
Laura-Ancuta Pop ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Drug Resistance ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Surface Receptors ◽  
Molecular Alterations ◽  
Mutational Pattern ◽  
Suitable Treatment

Abstract Background Triple negative breast cancer (TNBC) is a heterogeneous disease with aggressive behavior and an unfavorable prognosis rate. Due to the lack of surface receptors, TNBC must be intensely investigated in order to establish a suitable treatment for patients with this pathology. Chemoresistance is an important reason for therapeutic failure in TNBC. Method The aim of this study was to investigate the effect of doxorubicin in TNBC cell lines and to highlight cellular and molecular alterations after a long exposure to doxorubicin. Results The results revealed that doxorubicin significantly increased the half maximal inhibitory concentration (IC50) values at P12 and P24 compared to parenteral cells P0. Modifications in gene expression were investigated through microarray technique, and for detection of mutational pattern was used Next Generation Sequencing (NGS). 196 upregulated and 115 downregulated genes were observed as effect of multiple dose exposure, and 15 overexpressed genes were found to be involved in drug resistance. Also, the presence of some additional mutations in both cell lines was observed. Conclusion The outcomes of this research may provide novel biomarkers for drug resistance in TNBC. Also, this activity can highlight the potential mechanisms associated with drug resistance, as well as the potential therapies to counteract these mechanisms.

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