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

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 183 ◽  
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.

scholarly journals Data set of the protein expression profiles of Luminal A, Claudin-low and overexpressing HER2 + breast cancer cell lines by iTRAQ labelling and tandem mass spectrometry

Data in Brief ◽  
2015 ◽  
Vol 4 ◽  
pp. 292-301 ◽  
Author(s):  
Karla Grisel Calderón-González ◽  
Ma Luz Valero Rustarazo ◽  
Maria Luisa Labra-Barrios ◽  
César Isaac Bazán-Méndez ◽  
Alejandra Tavera-Tapia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Expression Profiles ◽  
Breast Cancer Cell Lines ◽  
Tandem Mass ◽  
Luminal A ◽  
Data Set ◽  
Her2 Breast Cancer ◽  
Protein Expression Profiles

scholarly journals MicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lisa Svartdal Normann ◽  
Miriam Ragle Aure ◽  
Suvi-Katri Leivonen ◽  
Mads Haugland Haugen ◽  
Vesa Hongisto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Targeted Treatment ◽  
Breast Cancer Cell Lines ◽  
Altered Expression ◽  
Her2 Breast Cancer

AbstractHER2-positive (HER2 +) breast cancer patients that do not respond to targeted treatment have a poor prognosis. The effects of targeted treatment on endogenous microRNA (miRNA) expression levels are unclear. We report that responsive HER2 + breast cancer cell lines had a higher number of miRNAs with altered expression after treatment with trastuzumab and lapatinib compared to poorly responsive cell lines. To evaluate whether miRNAs can sensitize HER2 + cells to treatment, we performed a high-throughput screen of 1626 miRNA mimics and inhibitors in combination with trastuzumab and lapatinib in HER2 + breast cancer cells. We identified eight miRNA mimics sensitizing cells to targeted treatment, miR-101-5p, mir-518a-5p, miR-19b-2-5p, miR-1237-3p, miR-29a-3p, miR-29c-3p, miR-106a-5p, and miR-744-3p. A higher expression of miR-101-5p predicted better prognosis in patients with HER2 + breast cancer (OS: p = 0.039; BCSS: p = 0.012), supporting the tumor-suppressing role of this miRNA. In conclusion, we have identified miRNAs that sensitize HER2 + breast cancer cells to targeted therapy. This indicates the potential of combining targeted drugs with miRNAs to improve current treatments for HER2 + breast cancers.

Backbone dihedral angles prediction servers for protein early-stage structure prediction

2019 ◽  
Vol 15 (4) ◽  
Author(s):  
Tomasz Smolarczyk ◽  
Katarzyna Stapor ◽  
Irena Roterman-Konieczna
Keyword(s):  
Protein Folding ◽  
Secondary Structure ◽  
Protein Function ◽  
Structure Prediction ◽  
Secondary Structure Prediction ◽  
Early Stage ◽  
Three Dimensional ◽  
Stage Structure ◽  
Dihedral Angles ◽  
Starting Point

AbstractThree-dimensional protein structure prediction is an important task in science at the intersection of biology, chemistry, and informatics, and it is crucial for determining the protein function. In the two-stage protein folding model, based on an early- and late-stage intermediates, we propose to use state-of-the-art secondary structure prediction servers for backbone dihedral angles prediction and devise an early-stage structure. Early-stage structures are used as a starting point for protein folding simulations, and any errors in this stage affect the final predictions. We have shown that modern secondary structure prediction servers could increase the accuracy of early-stage predictions compared to previously reported models.

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

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
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.

scholarly journals miR-342-5p as a Potential Regulator of HER2 Breast Cancer Cell Growth

MicroRNA ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 155-165 ◽  
Author(s):  
Evita Maria Lindholm ◽  
Suvi-Katri Leivonen ◽  
Eldri Undlien ◽  
Daniel Nebdal ◽  
Anna Git ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Breast Cancer Cell Lines ◽  
Nucleotide Exchange ◽  
Her2 Positive ◽  
Her2 Breast Cancer

Background: HER2 positive Breast Cancers (BC) have aggressive behavior and poor prognosis. Previously, we have identified miR-342-5p as an upstream regulator of HER2 signaling, as well as inhibitor of HER2 positive BC cell line growth. Objective: Here, we aimed to further investigate the molecular mechanisms behind miR-342-5pinduced HER2 pathway deregulation. </P><P> Method: Two HER2 amplified breast cancer cell lines were transiently transfected with miR-342-5p mimic or negative control, and gene expression was analyzed by Agilent microarrays. Three clinical datasets with BC patients were used to identify correlations between candidate genes and miR-342- 5p, and associations with survival. Results: Pathway analyses of all deregulated genes revealed a significant suppression of the HER2 downstream pathways ERK/MAPK and SAPK/JNK, whereas the miR-342-5p predicted target genes were enriched for pathways associated with cell motility.Biological functions linked to mitochondrial stability were ranked among the top toxicological functions in both gene lists. Among the most deregulated genes, Cytochrome B5 Reductase 3 (CYB5R3) and Rap Guanine Nucleotide Exchange Factor 6 (RAPGEF6) significantly anticorrelated and correlated, respectively, with miR-342-5p in all three clinical BC datasets. Low CYB5R3 levels and high RAPGEF6 levels were significantly associated with survival, although this was not directly associated with HER2 expression. Conclusion: Our data suggest that miR-342-5p overexpression in HER2 positive BC cell lines elicits broad effects on HER2 downstream signaling, cell motility and mitochondrial stability. Together these effects may render cells less proliferative and more sensitive to cellular stress.

scholarly journals Altered SERCA Expression in Breast Cancer

Medicina ◽  
2021 ◽  
Vol 57 (10) ◽  
pp. 1074
Author(s):  
Panayiota Christodoulou ◽  
Andreas Yiallouris ◽  
Artemis Michail ◽  
Maria-Ioanna Christodoulou ◽  
Panagiotis Politis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Expression Profiles ◽  
Regulatory Proteins ◽  
Breast Cancer Cell Lines ◽  
Breast Carcinomas ◽  
Cancer Breast ◽  
Pathological Conditions ◽  
Kaplan Meier ◽  
Cancer Types ◽  
Clinical Conditions

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.

scholarly journals A novel immune subtype classification of ER-positive, PR-negative and HER2-negative breast cancer based on the genomic and transcriptomic landscape

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Peiling Xie ◽  
Rui An ◽  
Shibo Yu ◽  
Jianjun He ◽  
Huimin Zhang
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Clinical Outcomes ◽  
Immune Escape ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Characteristics ◽  
Consensus Clustering ◽  
Breast Cancers ◽  
Her2 Breast Cancer

Abstract Background The diversity and plasticity behind ER+/PR−/HER2− breast cancer have not been widely explored. It is essential to identify heterogeneous microenvironment phenotypes and investigate specific genomic events driving the formation of these phenotypes. Methods Based on the immune-related gene expression profiles of 411 ER+/PR−/HER2− breast cancers in the METABRIC cohort, we used consensus clustering to identify heterogeneous immune subtypes and assessed their reproducibility in an independent meta-cohort including 135 patients collected from GEO database. We further analyzed the differences of cellular and molecular characteristics, and potential immune escape mechanism among immune subtypes. In addition, we constructed a transcriptional trajectory to visualize the distribution of individual patient. Results Our analysis identified and validated five reproducible immune subtypes with distinct cellular and molecular characteristics, potential immune escape mechanisms, genomic drivers, as well as clinical outcomes. An immune-cold subtype, with the least amount of lymphocyte infiltration, had a poorer prognosis. By contrast, an immune-hot subtype, which demonstrated the highest infiltration of CD8+ T cells, DCs and NK cells, and elevated IFN-γ response, had a comparatively favorable prognosis. Other subtypes showed more diverse gene expression and immune infiltration patterns with distinct clinical outcomes. Finally, our analysis revealed a complex immune landscape consisting of both discrete cluster and continuous spectrum. Conclusion Overall, this study revealed five heterogeneous immune subtypes among ER+/PR–/HER2− breast cancer, also provided important implications for clinical translations.

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