Exploring Molecular Pathways of Triple-Negative Breast Cancer

Ossovskaya, Valeria; Wang, Yipeng; Budoff, Adam; Xu, Qiang; Lituev, Alexander; Potapova, Olga; Vansant, Gordon; Monforte, Joseph; Daraselia, Nikolai

doi:10.1177/1947601911432496

Cited by 79 publications

(69 citation statements)

References 40 publications

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“…Furthermore, gene analysis showed that TNBC has a defined molecular signature and is regulated by the angiotensinogen molecular network, NF-κB, platelet-derived growth factor receptor, and p53 pathways, which are important in angiogenesis, cell-cycle regulation, and inflammation 47 .…”

Section: Discussionmentioning

confidence: 99%

Low Expression of Estrogen Receptor-α and Progesterone Receptor in Human Breast Cancer Tissues Is Associated With High-Grade Human Cytomegalovirus Protein Expression

Rahbar

Touma

Costa

et al. 2017

Clinical Breast Cancer

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MicroAbstractThe mechanisms involved in initiation and progression of breast cancer (BC), the most common malignancy and second leading cause of cancer deaths in women, are largely unknown. Human cytomegalovirus (HCMV) has been detected in primary BC, sentinel lymph nodes and brain metastases of BC patients. We found HCMV DNA, RNA, and proteins in BC, and their prevalence was higher in advanced cancer. HCMV levels correlated inversely with estrogen (P = 0.02) and progesterone (p = 0.003) receptor expression. HER2 expression was also found to

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Section: Discussionmentioning

confidence: 99%

Low Expression of Estrogen Receptor-α and Progesterone Receptor in Human Breast Cancer Tissues Is Associated With High-Grade Human Cytomegalovirus Protein Expression

Rahbar

Touma

Costa

et al. 2017

Clinical Breast Cancer

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“…Studies from gene expression profiling analysis revealed that the nuclear factor (NF)-jB pathway may represent a key regulator of TNBC (Ossovskaya et al, 2011). Activation of NF-jB signaling has been strongly implicated in the pathogenesis of certain TNBCs (Barbie et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

NF-κB Is a Potential Molecular Drug Target in Triple-Negative Breast Cancers

Poma

Labbozzetta

D’Alessandro

et al. 2017

OMICS: A Journal of Integrative Biology

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Breast cancer continues to cause significant burden in global health morbidity and mortality. Triple-negative breast cancers (TNBCs) are highly aggressive with poor prognosis and are characterized by lack of expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor (Her-2). TNBCs are often resistant to cytotoxic chemotherapy and pose major difficulty in achieving personalized medicine due to their molecular heterogeneity. There is increasing evidence that the aberrant activation of nuclear factor (NF)-jB signaling is a frequent characteristic of TNBCs. We evaluated the effects of different potential NF-jB inhibitors, such as bisindolylmaleimide I (BIS, a selective protein kinase C [PKC] inhibitor), MG132 (a proteasome inhibitor), curcumin (endowed with pleiotropic activities), and dehydroxymethylepoxyquinomicin (an inhibitor of NF-jB translocation into the nucleus) on the constitutive activation of NF-jB present in three TNBC cell lines (SUM 149, SUM 159, and MDA-MB-231). We also evaluated whether MDA-9/Syntenin plays a role in NF-jB activation, as observed in other cancer types. Indeed, silencing experiments with a siRNA anti-MDA-9/Syntenin produced a very strong reduction of NF-jB activation in all the three TNBC cell lines. We conclude that different approaches targeting NF-jB activation might potentially prove useful for innovation in anticancer drug development for TNBCs. Further research that bridge preclinical and clinical investigations with NF-jB inhibitors would be timely and warranted.

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“…TNBC is typically an aggressive cancer type displaying high rates of proliferation and metastasis and having generally poorer prognosis, particularly among those with advanced disease, as evidenced by increased recurrence and mortality compared with other breast cancer types [2]. Due to the lack of known therapeutic targets, such as ER, PR, and HER2 receptors, there are no specific therapies for TNBC tumors [3].…”

Section: Introductionmentioning

confidence: 99%

Dual specificity phosphatase 4 gene expression in association with triple-negative breast cancer outcome

Baglia

Cai

Zheng

et al. 2014

Breast Cancer Res Treat

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Purpose Triple-negative breast cancer (TNBC) is an aggressive cancer with limited treatment options. Dual specificity phosphatase 4 (DUSP4) has recently been suggested as a potential marker of chemotherapy resistance for TNBC. Methods DUSP4 gene expression levels were measured in breast cancer tissue from 469 TNBC patients aged 20 to 75 years who participated in the Shanghai Breast Cancer Survival Study and their association with recurrence/breast cancer mortality and total mortality was evaluated. Information on breast cancer diagnosis, treatment, and disease progression was collected via medical chart review and multiple in-person follow-up surveys. A Cox regression model was applied in the data analyses. Results Over a median follow-up of 5.3 years (range: 0.7-8.9 years), 100 deaths and 92 recurrences/breast cancer deaths were documented. Expression levels of transcript variant 1 (NM_001394) and transcript variant 2 (NM_057158) of the DUSP4 gene were studied and were highly correlated (r=0.76). Low DUSP4 expression levels, particularly of variant 1, were associated with both increased recurrence/breast cancer mortality and increased overall mortality. Hazard ratios with adjustment for age at diagnosis and TNM stage associated with below versus above the median expression level were 1.97 (95% confidence interval (CI): 1.27-3.05) for recurrence/breast cancer mortality and 2.09 (95% CI: 1.38-3.17) for overall mortality. Additional adjustment for expression levels of MKI67 and TP53, common treatment types, breast cancer subtype, and grade did not materially alter the observed associations. Conclusions Low DUSP4 expression levels predict recurrence and mortality in TNBC patients independently from known clinical and molecular predictors.

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Exploring Molecular Pathways of Triple-Negative Breast Cancer

Cited by 79 publications

References 40 publications

Low Expression of Estrogen Receptor-α and Progesterone Receptor in Human Breast Cancer Tissues Is Associated With High-Grade Human Cytomegalovirus Protein Expression

Low Expression of Estrogen Receptor-α and Progesterone Receptor in Human Breast Cancer Tissues Is Associated With High-Grade Human Cytomegalovirus Protein Expression

NF-κB Is a Potential Molecular Drug Target in Triple-Negative Breast Cancers

Dual specificity phosphatase 4 gene expression in association with triple-negative breast cancer outcome

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