scholarly journals Differential expression of the protein phosphatase 2 (PP2A) complex and breast cancer signature genes following suppression of mTOR signalling

2015 ◽  
Vol 26 ◽  
pp. iii15
Author(s):  
C. Saliba ◽  
S. Baldacchino ◽  
R. Gauci ◽  
M.P. Grixti ◽  
V. Petroni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Protein Phosphatase ◽  
Signature Genes ◽  
Protein Phosphatase 2 ◽  
Mtor Signalling

scholarly journals Differential expression of protein phosphatase 2 scaffold subunit A beta in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Survival Data ◽  
Protein Phosphatase ◽  
Normal Breast ◽  
Differentially Expressed ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
Subunit A ◽  
Protein Phosphatase 2

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding protein phosphatase 2 scaffold subunit A beta, PPP2R1B, when comparing primary tumors of the breast to the tissue of origin, the normal breast. PPP2R1B mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of PPP2R1B in primary tumors of the breast was correlated with recurrence-free survival in patients with luminal A subtype cancer, demonstrating a relationship between primary tumor expression of a differentially expressed gene and patient survival outcomes influenced by PAM50 molecular subtype. PPP2R1B may be of relevance to initiation, maintenance or progression of cancers of the female breast.

scholarly journals Differential expression of protein phosphatase 1 regulatory inhibitor subunit 1A in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Survival Data ◽  
Protein Phosphatase ◽  
Differentially Expressed Gene ◽  
Normal Breast ◽  
Differentially Expressed ◽  
Protein Phosphatase 1 ◽  
Significant Differential Expression ◽  
Primary Tumors

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding protein phosphatase 1 regulatory inhibitor subunit 1A, PPP1R1A, when comparing primary tumors of the breast to the tissue of origin, the normal breast. PPP1R1A mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of PPP1R1A in primary tumors of the breast was correlated with overall survival in patients with basal-like and luminal A subtype cancer, demonstrating a relationship between primary tumor expression of a differentially expressed gene and patient survival outcomes influenced by PAM50 molecular subtype. PPP1R1A may be of relevance to initiation, maintenance or progression of cancers of the female breast.

scholarly journals Differential expression of protein phosphatase 2A activator in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Normal Breast ◽  
Recurrence Free Survival ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
Free Survival ◽  
Phosphatase 2A

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding protein phosphatase 2A activator, PPP2R4, also known as PTPA (protein phosphatase 2 phosphatase activator) when comparing primary tumors of the breast to the tissue of origin, the normal breast. PPP2R4 mRNA was present at significantly higher quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of PPP2R4 in primary tumors of the breast was correlated with recurrence-free survival in patients with basal and luminal B type cancers, but in a contrary manner, demonstrating a complex relationship between correlation of primary tumor expression with recurrence-free survival based on molecular subtype. PPP2R4 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

Differential expression and androgen regulation of microRNA molecules in breast cancer cells

2016 ◽  
Author(s):  
Mamoun Ahram ◽  
Rand Zaza ◽  
Ebtihal Mustafa ◽  
Heba Jarrar ◽  
Razan Al-Saber ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Differential Expression ◽  
Breast Cancer Cells ◽  
Androgen Regulation

Identifying Breast Cancer-induced gene perturbations and its application in guiding drug repurposing

2020 ◽  
Vol 15 ◽  
Author(s):  
Jujuan Zhuang ◽  
Shuang Dai ◽  
Lijun Zhang ◽  
Pan Gao ◽  
Yingmin Han ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Enrichment Analysis ◽  
Cancer Tissue ◽  
Connectivity Analysis ◽  
Cancer Drugs ◽  
Normal Tissues ◽  
Differential Gene ◽  
Differential Modules ◽  
Differential Connectivity

Background: Breast cancer is a complex disease with high prevalence in women, the molecular mechanisms of which are still unclear at present. Most transcriptomic studies on breast cancer focus on differential expression of each gene between tumor and the adjacent normal tissues, while the other perturbations induced by breast cancer including the gene regulation variations, the changes of gene modules and the pathways, which might be critical to the diagnosis, treatment and prognosis of breast cancer are more or less ignored. Objective: We presented a complete process to study breast cancer from multiple perspectives, including differential expression analysis, constructing gene co-expression networks, modular differential connectivity analysis, differential gene connectivity analysis, gene function enrichment analysis key driver analysis. In addition, we prioritized the related anti-cancer drugs based on enrichment analysis between differential expression genes and drug perturbation signatures. Methods: The RNA expression profiles of 1109 breast cancer tissue and 113 non-tumor tissues were downloaded from The Cancer Genome Atlas (TCGA) database. Differential expression of RNAs was identified using the “DESeq2” bioconductor package in R, and gene co-expression networks was constructed using the weighted gene co-expression network analysis (WGCNA). To compare the module changes and gene co-expression variations between tumor and the adjacent normal tissues, modular differential connectivity (MDC) analysis and differential gene connectivity analysis (DGCA) were performed. Results: Top differential genes like MMP11 and COL10A1 were known to be associated with breast cancer. And we found 23 modules in the tumor network had significantly different co-expression patterns. The top differential modules were enriched in Goterms related to breast cancer like MHC protein complex, leukocyte activation, regulation of defense response and so on. In addition, key genes like UBE2T driving the top differential modules were significantly correlated with the patients’ survival. Finally, we predicted some potential breast cancer drugs, such as Eribulin, Taxane, Cisplatin and Oxaliplatin. Conclusion: As an indication, this framework might be useful in understanding the molecular pathogenesis of diseases like breast cancer and inferring useful drugs for personalized medication

scholarly journals MicroRNA-527 Induces Proliferation and Cell Cycle in Esophageal Squamous Cell Carcinoma Cells by Repressing PH Domain Leucine-Rich-Repeats Protein Phosphatase 2

Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582092868 ◽  
Author(s):  
Qingjie Xian ◽  
Ronglei Zhao ◽  
Juanjuan Fu
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Squamous Cell ◽  
Protein Phosphatase ◽  
Ph Domain ◽  
Gene Reporter Assay ◽  
Protein Phosphatase 2

Increasing evidence indicated that microRNAs served dominant roles in carcinogenesis and cancer progression by targeting potential downstream genes. In our study, we found that miR-527 was an upregulated expression in human esophageal squamous cell carcinoma (ESCC) cells and tissues. Furthermore, overexpression of miR-527 promoted cell proliferation and colony formation, enhanced anchorage-independent growth ability, and contributed to cell cycle. In addition, protein phosphatase 2 (PHLPP2) was identified as the direct downstream target gene of miR-527 and was confirmed by luciferase gene reporter assay. In summary, we concluded that miR-527 acted as an oncogenic microRNA in ESCC development by directly targeting PHLPP2 might be a novel therapeutic target for the treatment of ESCC.

scholarly journals Prognostic gene expression signatures of breast cancer are lacking a sensible biological meaning

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kalifa Manjang ◽  
Shailesh Tripathi ◽  
Olli Yli-Harja ◽  
Matthias Dehmer ◽  
Galina Glazko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Progression ◽  
Disease Etiology ◽  
Signature Genes ◽  
Biological Meaning ◽  
Gene Sets ◽  
Breast Cancer Outcome ◽  
Biological Interpretation ◽  
Pathological Behavior

AbstractThe identification of prognostic biomarkers for predicting cancer progression is an important problem for two reasons. First, such biomarkers find practical application in a clinical context for the treatment of patients. Second, interrogation of the biomarkers themselves is assumed to lead to novel insights of disease mechanisms and the underlying molecular processes that cause the pathological behavior. For breast cancer, many signatures based on gene expression values have been reported to be associated with overall survival. Consequently, such signatures have been used for suggesting biological explanations of breast cancer and drug mechanisms. In this paper, we demonstrate for a large number of breast cancer signatures that such an implication is not justified. Our approach eliminates systematically all traces of biological meaning of signature genes and shows that among the remaining genes, surrogate gene sets can be formed with indistinguishable prognostic prediction capabilities and opposite biological meaning. Hence, our results demonstrate that none of the studied signatures has a sensible biological interpretation or meaning with respect to disease etiology. Overall, this shows that prognostic signatures are black-box models with sensible predictions of breast cancer outcome but no value for revealing causal connections. Furthermore, we show that the number of such surrogate gene sets is not small but very large.

scholarly journals Deregulation of protein phosphatase 2A inhibitor SET is associated with malignant progression in breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katsunori Tozuka ◽  
Pattama Wongsirisin ◽  
Shigenori E. Nagai ◽  
Yasuhito Kobayashi ◽  
Miki Kanno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Recurrent Breast Cancer ◽  
Stage I ◽  
Breast Cancer Patients ◽  
Potential Biomarker ◽  
Phosphatase 2A ◽  
Mcf 7

AbstractTo understand the mechanism underlying metastasis, identification of a mechanism-based and common biomarker for circulating tumour cells (CTCs) in heterogenous breast cancer is needed. SET, an endogenous inhibitor of protein phosphatase 2A, was overexpressed in all subtypes of invasive breast carcinoma tissues. Treatment with SET-targeted siRNAs reduced the motility of MCF-7 and MDA-MB-231 cells in transwell assay. SET knockdown reduced the number of mammospheres by 60–70% in MCF-7 and MDA-MB-231 cells, which was associated with the downregulation of OCT4 and SLUG. Hence, we analysed the presence of SET-expressing CTCs (SET-CTCs) in 24 breast cancer patients. CTCs were enriched using a size-based method and then immunocytochemically analysed using an anti-SET antibody. SET-CTCs were detected in 6/6 (100%) patients with recurrent breast cancer with a median value of 12 (12 cells/3 mL blood), and in 13/18 (72.2%) patients with stage I–III breast cancer with a median value of 2.5, while the median value of healthy controls was 0. Importantly, high numbers of SET-CTCs were correlated with lymph node metastasis in patients with stage I–III disease. Our results indicate that SET contributes to breast cancer progression and can act as a potential biomarker of CTCs for the detection of metastasis.

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