scholarly journals SUN-008 The Glucocorticoid Receptor Is Essential For TGFβ and p38 MAPK Mediated Cancer Phenotypes in Triple Negative Breast Cancer

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Carlos Perez Kerkvliet ◽  
Amy Dwyer ◽  
Tarah Regan Anderson ◽  
Marissa Oram ◽  
Branden Smeester ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucocorticoid Receptor ◽  
P38 Mapk ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cancer Phenotypes

scholarly journals ATG9A Is Overexpressed in Triple Negative Breast Cancer and Its In Vitro Extinction Leads to the Inhibition of Pro-Cancer Phenotypes

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 248 ◽  
Author(s):  
Aurore Claude-Taupin ◽  
Leïla Fonderflick ◽  
Thierry Gauthier ◽  
Laura Mansi ◽  
Jean-René Pallandre ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cancer Cell Line ◽  
Cancer Tissue ◽  
The Future ◽  
Cancer Phenotypes

Early detection and targeted treatments have led to a significant decrease in mortality linked to breast cancer (BC), however, important issues need to be addressed in the future. One of them will be to find new triple negative breast cancer (TNBC) therapeutic strategies, since none are currently efficiently targeting this subtype of BC. Since numerous studies have reported the possibility of targeting the autophagy pathway to treat or limit cancer progression, we analyzed the expression of six autophagy genes (ATG9A, ATG9B, BECLIN1, LC3B, NIX and P62/SQSTM1) in breast cancer tissue, and compared their expression with healthy adjacent tissue. In our study, we observed an increase in ATG9A mRNA expression in TNBC samples from our breast cancer cohort. We also showed that this increase of the transcript was confirmed at the protein level on paraffin-embedded tissues. To corroborate these in vivo data, we designed shRNA- and CRISPR/Cas9-driven inhibition of ATG9A expression in the triple negative breast cancer cell line MDA-MB-436, in order to determine its role in the regulation of cancer phenotypes. We found that ATG9A inhibition led to an inhibition of in vitro cancer features, suggesting that ATG9A can be considered as a new marker of TNBC and might be considered in the future as a target to develop new specific TNBC therapies.

scholarly journals Glucocorticoid Receptor Antagonism as a Novel Therapy for Triple-Negative Breast Cancer

2013 ◽  
Vol 19 (22) ◽  
pp. 6163-6172 ◽  
Author(s):  
Maxwell N. Skor ◽  
Erin L. Wonder ◽  
Masha Kocherginsky ◽  
Anju Goyal ◽  
Ben A. Hall ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucocorticoid Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Novel Therapy ◽  
Receptor Antagonism

Genotypic characterization of phenotypically defined triple-negative breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 500-500 ◽  
Author(s):  
J. A. Sparano ◽  
L. J. Goldestin ◽  
B. H. Childs ◽  
S. Shak ◽  
S. Badve ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Triple Negative Breast Cancer ◽  
Intracellular Signaling ◽  
Triple Negative ◽  
Phenotypic Characterization ◽  
Breast Cancers ◽  
Nucleosome Assembly ◽  
Expression Of Genes ◽  
Cancer Phenotypes

500 Background: Triple negative breast cancer (TNBC) is associated with a higher risk of recurrence and earlier recurrences than other breast cancer phenotypes. We evaluated the genotypic features of TNBC compared with hormone receptor (HR)-positive disease, and also evaluated genotypic features associated with recurrence. Methods: RNA extracted from tumor samples obtained from 764 patients with stage I-III breast cancer was analyzed by RT-PCR for 371 genes. All patients received adjuvant chemotherapy (plus hormonal therapy in HR-positive disease) in trial E2197; HR and HER2 expression were evaluated by immunohistochemistry (IHC) in a central lab (J Clin Oncol 26:2473–2481). An unsupervised clustering analysis was performed in all samples (N=764). Cox proportional hazard models were used to identify differences in gene expression in TNBC versus HR-positive disease, and with recurrence in phenotypically defined (by IHC) TNBC (N=246) and HR-positive (N=465) disease. Results: Unsupervised analysis revealed two major clusters that differed with regard to HR expression by IHC. Supervised analysis comparing the TNBC vs. HR-positive phenotypes revealed 269 genes (73%) with significantly different expression (p<0.0001). The top 10% of genes exhibiting higher expression the TN group included genes associated with nucleosome assembly (CENPA), kinase activity (TTK), cell division (KIFC2), proliferation (BUB1), intracellular signaling (DEPDC1), DNA repair (CHK1), anti-apoptosis (GSTP1), and transcriptional regulation (MYBL2). There was increased expression of genes for which inhibitors are currently being evaluated, including AURKB and CHK1 in TNBC, and IGF1R and RhoC in HR-positive disease. Although GRB7 expression was significantly lower in the TN group, increased expression of GRB7 was the only gene in the TNBC group (but not the HR-positive group) associated with increased recurrence (p=0.04), and did not correlate with nodal status, tumor size, or grade. Conclusions: We genotypically characterized breast cancers that have also undergone rigorous phenotypic characterization.. There were significant differences in gene expression between the TN and HR-positive groups, including genes for which targeted agents are currently being evaluated in the clinic. [Table: see text]

scholarly journals Pseudopterosin Inhibits Proliferation and 3D Invasion in Triple Negative Breast Cancer by Agonizing Glucocorticoid Receptor Alpha

2018 ◽  
Author(s):  
Julia Sperlich ◽  
Nicole Teusch
Keyword(s):  
Breast Cancer ◽  
Glucocorticoid Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Mononuclear Cells ◽  
Biological Activities ◽  
Tumor Spheroids ◽  
Peripheral Blood Mononuclear ◽  
Surrounding Matrix ◽  
Novel Approach

Pseudopterosin, produced by the sea whip of the genus Antillogorgia, possesses a variety of promising biological activities including potent anti-inflammatory effects. However, few studies examined pseudopterosin in the treatment of cancer cells and, to our knowledge, the ability to inhibit triple negative breast cancer (TNBC) proliferation or invasion has not been explored. Thus, we evaluated the as yet unknown mechanism of action of pseudopterosin: Pseudopterosin was able to inhibit proliferation of TNBC. Interestingly, analyzing breast cancer cell proliferation after knocking down glucocorticoid receptor &alpha; (GR&alpha;) revealed that anti-proliferative effects of pseudopterosin were significantly inhibited when GR&alpha; expression was reduced. Furthermore, pseudopterosin inhibited invasion of MDA-MB-231 3D tumor spheroids embedded in an extracellular-like matrix. Remarkably, the knockdown of GR&alpha; in 3D tumor spheroids revealed increased ability of cells to invade the surrounding matrix. In a co-culture, encompassing peripheral blood mononuclear cells (PBMC) and MDA-MB-231 cells, production of interleukin 6 (IL-6) and interleukin 8 (IL-8) significantly increased compared to monoculture. Notably, pseudopterosin proved to block cytokine elevation, representing key players in tumor progression, in the co-culture. Thus, our results reveal pseudopterosin treatment as a potential novel approach in TNBC therapy.

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