scholarly journals Blockade of PD-1, PD-L1, and TIM-3 Altered Distinct Immune- and Cancer-Related Signaling Pathways in the Transcriptome of Human Breast Cancer Explants

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 703
Author(s):  
Reem Saleh ◽  
Salman M. Toor ◽  
Dana Al-Ali ◽  
Varun Sasidharan Nair ◽  
Eyad Elkord
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Checkpoint Inhibitors ◽  
Rna Seq ◽  
Human Breast ◽  
Compensatory Mechanisms ◽  
Transcriptomic Data ◽  
Functional Studies ◽  
Programmed Death ◽  
Cell Death Protein

Immune checkpoint inhibitors (ICIs) are yet to have a major advantage over conventional therapies, as only a fraction of patients benefit from the currently approved ICIs and their response rates remain low. We investigated the effects of different ICIs—anti-programmed cell death protein 1 (PD-1), anti-programmed death ligand-1 (PD-L1), and anti-T cell immunoglobulin and mucin-domain containing-3 (TIM-3)—on human primary breast cancer explant cultures using RNA-Seq. Transcriptomic data revealed that PD-1, PD-L1, and TIM-3 blockade follow unique mechanisms by upregulating or downregulating distinct pathways, but they collectively enhance immune responses and suppress cancer-related pathways to exert anti-tumorigenic effects. We also found that these ICIs upregulated the expression of other IC genes, suggesting that blocking one IC can upregulate alternative ICs, potentially giving rise to compensatory mechanisms by which tumor cells evade anti-tumor immunity. Overall, the transcriptomic data revealed some unique mechanisms of the action of monoclonal antibodies (mAbs) targeting PD-1, PD-L1, and TIM-3 in human breast cancer explants. However, further investigations and functional studies are warranted to validate these findings.

Structural and functional studies of insulin receptors in human breast cancer

1993 ◽  
Vol 25 (1) ◽  
pp. 73-82 ◽  
Author(s):  
Lucia Frittitta ◽  
Riccardo Vigneri ◽  
Vincenzo Papa ◽  
Ira D. Goldfine ◽  
Giuseppe Grasso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Insulin Receptors ◽  
Human Breast ◽  
Functional Studies

scholarly journals A combined approach with gene-wise normalization improves the analysis of RNA-seq data in human breast cancer subtypes

PLoS ONE ◽  
2018 ◽  
Vol 13 (8) ◽  
pp. e0201813 ◽  
Author(s):  
Xiaohong Li ◽  
Eric C. Rouchka ◽  
Guy N. Brock ◽  
Jun Yan ◽  
Timothy E. O’Toole ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Breast Cancer Subtypes ◽  
Combined Approach ◽  
Rna Seq ◽  
Human Breast ◽  
Cancer Subtypes

scholarly journals Identification of a Modified HOXB9 mRNA in Breast Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ayako Nakashoji ◽  
Tetsu Hayashida ◽  
Yuko Kawai ◽  
Masayuki Kikuchi ◽  
Rurina Watanuki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Cancer Cell Line ◽  
Clinical Samples ◽  
The Novel ◽  
Rna Seq ◽  
Human Breast ◽  
Aberrant Expression ◽  
Novel Variant

First identified as a developmental gene, HOXB9 is also known to be involved in tumor biological processes, and its aberrant expression correlates with poor prognosis of various cancers. In this study, we isolated a homeodomain-less, novel HOXB9 variant (HOXB9v) from human breast cancer cell line-derived mRNA. We confirmed that the novel variant was produced from variationless HOXB9 genomic DNA. RT-PCR of mRNA isolated from clinical samples and reanalysis of publicly available RNA-seq data proved that the new transcript is frequently expressed in human breast cancer. Exogenous HOXB9v expression significantly enhanced the proliferation of breast cancer cells, and gene ontology analysis indicated that apoptotic signaling was suppressed in these cells. Considering that HOXB9v lacks key domains of homeobox proteins, its behavior could be completely different from that of the previously described variationless HOXB9. Because none of the previous studies on HOXB9 have considered the presence of HOXB9v, further research analyzing the two transcripts individually is warranted to re-evaluate the true role of HOXB9 in cancer.

scholarly journals Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer

2014 ◽  
Vol 146 (1) ◽  
pp. 15-24 ◽  
Author(s):  
S. Muenst ◽  
A. R. Schaerli ◽  
F. Gao ◽  
S. Däster ◽  
E. Trella ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Poor Prognosis ◽  
Human Breast ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

scholarly journals Novel mechanistic targets of Forkhead box Q1 transcription factor in human breast cancer cells

2020 ◽  
Author(s):  
Su-Hyeong Kim ◽  
Eun-Ryeong Hahm ◽  
Krishna B. Singh ◽  
Shivendra V. Singh
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Rna Seq ◽  
Human Breast ◽  
Forkhead Box ◽  
Luminal Type ◽  
Mcf 7

The transcription factor forkhead box Q1 (FoxQ1), which is overexpressed in different solid tumors, has emerged as a key player in the pathogenesis of breast cancer by regulating epithelial-mesenchymal transition, maintenance of cancer-stem like cells, and metastasis. However, the mechanism underlying oncogenic function of FoxQ1 is still not fully understood. In this study, we compared the RNA-seq data from FoxQ1 overexpressing SUM159 cells with that of empty vector-transfected control (EV) cells to identify novel mechanistic targets of this transcription factor. Consistent with published results in basal-like subtype, immunohistochemistry revealed upregulation of FoxQ1 protein in luminal-type human breast cancer tissue microarrays when compared to normal mammary tissues. Many previously reported transcriptional targets of FoxQ1 (e.g., E-cadherin, N-cadherin, fibronectin 1, etc.) were verified from the RNA-Seq analysis. FoxQ1 overexpression resulted in downregulation of genes associated with cell cycle checkpoints, M phase, and cellular response to stress/external stimuli as evidenced from the Reactome pathway analysis. Consequently, FoxQ1 overexpression resulted in S, G2M and mitotic arrest in basal-like SUM159 and HMLE cells, but not in luminal-type MCF-7 cells. There were differences in expression of cell cycle-associated proteins between FoxQ1 overexpressing SUM159 and MCF-7 cells. Finally, we show for the first time that FoxQ1 is a direct transcriptional regulator of interleukin (IL)-1α, IL-8, and vascular endothelial growth factor in breast cancer cells. Chromatin immunoprecipitation revealed FoxQ1 occupancy at the promoters of IL-1α, IL-8, and VEGF. In conclusion, the present study reports novel mechanistic targets of FoxQ1 in human breast cancer cells.

scholarly journals Mechanistic Targets of Diallyl Trisulfide in Human Breast Cancer Cells Identified by RNA-seq Analysis

2021 ◽  
Vol 26 (2) ◽  
pp. 128-136
Author(s):  
Eun-Ryeong Hahm ◽  
Su-Hyeong Kim ◽  
Sivapar V. Mathan ◽  
Rana P. Singh ◽  
Shivendra V. Singh
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Diallyl Trisulfide ◽  
Rna Seq ◽  
Human Breast Cancer Cells ◽  
Human Breast
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