Altered SERCA Expression in Breast Cancer

Background and Objectives: Calcium (Ca2+) signaling is critical for the normal functioning of various cellular activities. However, abnormal changes in cellular Ca2+ can contribute to pathological conditions, including various types of cancer. The maintenance of intracellular Ca2+ levels is achieved through tightly regulated processes that help maintain Ca2+ homeostasis. Several types of regulatory proteins are involved in controlling intracellular Ca2+ levels, including the sarco/endoplasmic reticulum (SR/ER) Ca2+ ATPase pump (SERCA), which maintains Ca2+ levels released from the SR/ER. In total, three ATPase SR/ER Ca2+-transporting (ATP2A) 1-3 genes exist, which encode for several isoforms whose expression profiles are tissue-specific. Recently, it has become clear that abnormal SERCA expression and activity are associated with various types of cancer, including breast cancer. Breast carcinomas represent 40% of all cancer types that affect women, with a wide variety of pathological and clinical conditions. Results: The present study found significantly different SERCA specific-type expressions in a series of breast cancer cell lines. Moreover, bioinformatics analysis indicated that ATP2A1 and ATP2A3 expression was highly altered in patients with breast cancer. Methodology: Using cBioPortal breast cancer patient data, Kaplan–Meier plots demonstrated that high ATP2A1 and ATP2A3 expression was associated with reduced patient survival. Conclusion: Overall, the present data suggest that SERCA gene-specific expressioncan possibly be considered as a crucial target for the control of breast cancer development and progression.

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Structure–Activity Relationship of HER2 Receptor Targeting Peptide and Its Derivatives in Targeted Tumor Therapy

Biomolecules ◽

10.3390/biom10020183 ◽

2020 ◽

Vol 10 (2) ◽

pp. 183 ◽

Cited By ~ 1

Author(s):

Biri-Kovács ◽

Adorján ◽

Szabó ◽

Szeder ◽

Bősze ◽

...

Keyword(s):

Breast Cancer ◽

Structure Prediction ◽

Secondary Structure Prediction ◽

Expression Profiles ◽

Tumor Therapy ◽

Breast Cancer Cell Lines ◽

Tyrosine Kinase Receptor ◽

Her2 Breast Cancer ◽

Extracellular Region ◽

Starting Point

Human epidermal growth factor (HER2) is a transmembrane tyrosine kinase receptor that is frequently overexpressed in breast cancer. Its increased level prognoses a poor patient outcome and a high mortality rate. Despite the widening spectrum of therapies that are becoming available to treat HER2+ breast cancer, its side effects and resistance still make this protein a valuable object of research in targeted tumor therapy. The role of tumor-targeting peptides has become more and more prominent in the last few decades due to their simple synthesis and pharmakokinetic properties. Here, we examine two fluorescently-labeled HER2-specific peptides and their combined analogues that are developed to target the extracellular region of HER2. The peptides are investigated on breast cancer cell lines with different HER2 expression profiles. Moreover, their extracellular localization and specificity are confirmed by flow cytometry and confocal microscopy. Therefore, a new, combined HER2 binding conjugate is obtained that interacts with HER2-overexpressing cells with high affinity and specificity. Furthermore, secondary structure prediction reveals that the α-helical content of the peptides is associated with their receptor recognition. This highly specific conjugate can be used as a starting point for diagnostical or drug-targeting purposes in upcoming studies.

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Deciphering the Correlation between Breast Tumor Samples and Cell Lines by Integrating Copy Number Changes and Gene Expression Profiles

BioMed Research International ◽

10.1155/2015/901303 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Yi Sun ◽

Qi Liu

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Breast Tumors ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Tumor Group

Breast cancer is one of the most common cancers with high incident rate and high mortality rate worldwide. Although different breast cancer cell lines were widely used in laboratory investigations, accumulated evidences have indicated that genomic differences exist between cancer cell lines and tissue samples in the past decades. The abundant molecular profiles of cancer cell lines and tumor samples deposited in the Cancer Cell Line Encyclopedia and The Cancer Genome Atlas now allow a systematical comparison of the breast cancer cell lines with breast tumors. We depicted the genomic characteristics of breast primary tumors based on the copy number variation and gene expression profiles and the breast cancer cell lines were compared to different subgroups of breast tumors. We identified that some of the breast cancer cell lines show high correlation with the tumor group that agrees with previous knowledge, while a big part of them do not, including the most used MCF7, MDA-MB-231, and T-47D. We presented a computational framework to identify cell lines that mostly resemble a certain tumor group for the breast tumor study. Our investigation presents a useful guide to bridge the gap between cell lines and tumors and helps to select the most suitable cell line models for personalized cancer studies.

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Abstract P5-05-09: Systemic perturbations induced by all-trans retinoic acid in the gene-expression profiles of sixteen breast cancer cell lines characterized by sensitivity and resistance to the anti-proliferative effects of the retinoid

10.1158/1538-7445.sabcs18-p5-05-09 ◽

2019 ◽

Author(s):

E Garattini ◽

M Bolis ◽

A Vallerga ◽

M Fratelli ◽

G Paroni ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Retinoic Acid ◽

Cell Lines ◽

Breast Cancer Cell ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Breast Cancer Cell Lines ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid

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Analysis of the Gene Expression Profile of Stromal Pro-Tumor Factors in Cancer-Associated Fibroblasts from Luminal Breast Carcinomas

Diagnostics ◽

10.3390/diagnostics10110865 ◽

2020 ◽

Vol 10 (11) ◽

pp. 865 ◽

Cited By ~ 1

Author(s):

Noemi Eiro ◽

Sandra Cid ◽

María Fraile ◽

Jorge Ruben Cabrera ◽

Luis O. Gonzalez ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Cancer Associated Fibroblasts ◽

Breast Carcinomas ◽

Luminal A ◽

Luminal B

Luminal tumors are the most frequent type of breast carcinomas showing less tumor aggressiveness, although heterogeneity exists in their clinical outcomes. Cancer-associated fibroblasts (CAFs) are a key component of the tumor stroma which contribute to tumor progression. We investigated by real-time PCR the gene expression of 19 factors implicated in tumor progression. Those factors included the calcium-binding protein S100A4, several growth factors (FGF2, FGF7, HGF, PDGFA, PDGFB, TGFβ, VEGFA, and IGF2), and we also studied inflammatory cytokines (IL6 and IL8), chemokines (CCL2, CXCL12), important proteases (uPA, MMP2, MMP9 and MMP11), the nuclear factor NFκB, and the metalloprotease inhibitor TIMP1, from luminal A and luminal B breast carcinoma CAFs. We performed a similar analysis after co-culturing CAFs with MCF-7 and MDA-MB-231 breast cancer cell lines. MMP-9 and CCL2 gene expressions were higher in CAFs from luminal B tumors. We also found different patterns in the induction of pro-tumoral factors from different CAFs populations co-cultured with different cancer cell lines. Globally, CAFs from luminal B tumors showed a higher expression of pro-tumor factors compared to CAFs from luminal A tumors when co-cultured with breast cancer cell lines. Moreover, we found that CAFs from metastatic tumors had higher IGF-2 gene expression, and we detected the same after co-culture with cell lines. Our results show the variability in the capacities of CAFs from luminal breast carcinomas, which may contribute to a better biological and clinical characterization of these cancer subtypes.

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Targeting Metabolic Reprogramming to Improve Breast Cancer Treatment: An In Vitro Evaluation of Selected Metabolic Inhibitors Using a Metabolomic Approach

Metabolites ◽

10.3390/metabo11080556 ◽

2021 ◽

Vol 11 (8) ◽

pp. 556

Author(s):

Anaïs Draguet ◽

Vanessa Tagliatti ◽

Jean-Marie Colet

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

In Vitro Study ◽

Metabolic Reprogramming ◽

World Health ◽

Metabolic Inhibitors ◽

Breast Cancer Cell Lines ◽

Cell Mortality ◽

Cancer Types

Characteristic metabolic adaptations are recognized as a cancer hallmark. Breast cancer, like other cancer types, displays cellular respiratory switches—in particular, the Warburg effect—and important fluctuations in the glutamine and choline metabolisms. This cancer remains a world health issue mainly due to the side effects associated with chemotherapy, which force a reduction in the administered dose or even a complete discontinuation of the treatment. For example, Doxorubicin is efficient to treat breast cancer but unfortunately induces severe cardiotoxicity. In the present in vitro study, selected metabolic inhibitors were evaluated alone or in combination as potential treatments against breast cancer. In addition, the same inhibitors were used to possibly potentiate the effects of Doxorubicin. As a result, the combination of CB-839 (glutaminase inhibitor) and Oxamate (lactate dehydrogenase inhibitor) and the combination of CB-839/Oxamate/D609 (a phosphatidylcholine-specific phospholipase C inhibitor) caused significant cell mortality in both MDA-MB-231 and MCF-7, two breast cancer cell lines. Furthermore, all inhibitors were able to improve the efficacy of Doxorubicin on the same cell lines. Those findings are quite encouraging with respect to the clinical goal of reducing the exposure of patients to Doxorubicin and, subsequently, the severity of the associated cardiotoxicity, while keeping the same treatment efficacy.

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Evaluation of Biochemical Markers Correlated with Breast Cancer Young Patients

Revista de Chimie ◽

10.37358/rc.20.8.8298 ◽

2020 ◽

Vol 71 (8) ◽

pp. 255-260

Author(s):

Xenia Bacinschi ◽

Oana Saptefrati ◽

Anca Zgura ◽

Laura Iliescu ◽

Bogdan Haineala ◽

...

Keyword(s):

Breast Cancer ◽

Pearson Correlation ◽

Young Patients ◽

Breast Carcinomas ◽

Material Resources ◽

Cancer Breast ◽

Incidence And Mortality ◽

Long Time ◽

Invasive Breast Carcinomas

Breast cancer ranks first in women in terms incidence and mortality in the world. In Romania its frequency continues to increase and now is the most common cancer in the women. Despite therapeutic advances, there is still severe cancer with heavy sequelae both physical and mental. It`s even harder to accept or even reject when it comes to a young women. For a long time, breast cancer was linked to a more or less old age. However, in the recent literature, breast cancer is on the rise more observed in a young population, its frequency is estimated at 7% all cases of breast cancer. Breast cancer diagnosed in young patients tends to be more aggressive than the rest of the cases. In this paper, we present the results of a study that included 59 women presenting primary invasive breast carcinomas selected from the database of the Institute of Oncology Bucharest in which clinical follow-up data cover long intervals of time (2014 - 2019) and whose histological pieces met technical conditions optimal for extended immunohistochemical processing. The available material resources allowed the completion of a complete analyzes in all cases in relation to the immunohistochemical examination . The correlation between the expression of each of the antibodies was calculated using Pearson correlation coefficient.

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Multi-Omics Characterization of the Spontaneous Mesenchymal–Epithelial Transition in the PMC42 Breast Cancer Cell Lines

Journal of Clinical Medicine ◽

10.3390/jcm8081253 ◽

2019 ◽

Vol 8 (8) ◽

pp. 1253 ◽

Cited By ~ 4

Author(s):

Sugandha Bhatia ◽

James Monkman ◽

Tony Blick ◽

Pascal HG Duijf ◽

Shivashankar H. Nagaraj ◽

...

Keyword(s):

Breast Cancer ◽

Phenotypic Plasticity ◽

Cell Line ◽

Cell Lines ◽

Daughter Cell ◽

Cancer Metastasis ◽

Expression Profiles ◽

Breast Cancer Cell Lines ◽

Mesenchymal Transition ◽

Mesenchymal Epithelial Transition

Epithelial–mesenchymal plasticity (EMP), encompassing epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition (MET), are considered critical events for cancer metastasis. We investigated chromosomal heterogeneity and chromosomal instability (CIN) profiles of two sister PMC42 breast cancer (BC) cell lines to assess the relationship between their karyotypes and EMP phenotypic plasticity. Karyotyping by GTG banding and exome sequencing were aligned with SWATH quantitative proteomics and existing RNA-sequencing data from the two PMC42 cell lines; the mesenchymal, parental PMC42-ET cell line and the spontaneously epithelially shifted PMC42-LA daughter cell line. These morphologically distinct PMC42 cell lines were also compared with five other BC cell lines (MDA-MB-231, SUM-159, T47D, MCF-7 and MDA-MB-468) for their expression of EMP and cell surface markers, and stemness and metabolic profiles. The findings suggest that the epithelially shifted cell line has a significantly altered ploidy of chromosomes 3 and 13, which is reflected in their transcriptomic and proteomic expression profiles. Loss of the TGFβR2 gene from chromosome 3 in the epithelial daughter cell line inhibits its EMT induction by TGF-β stimulus. Thus, integrative ‘omics’ characterization established that the PMC42 system is a relevant MET model and provides insights into the regulation of phenotypic plasticity in breast cancer.

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