scholarly journals Nanolipoprotein mediated Her2 protein transfection induces malignant transformation in human breast acinar cultures

2020 ◽  
Author(s):  
Wei He ◽  
Angela C. Evans ◽  
Matthew Coleman ◽  
Claire Robertson
Keyword(s):  
Breast Cancer ◽  
Malignant Transformation ◽  
Cell Surface Receptor ◽  
Cell Phenotype ◽  
Her2 Overexpression ◽  
Malignant Cells ◽  
Transformation Techniques ◽  
Her2 Protein ◽  
Surface Receptor ◽  
Protein Transfection

AbstractHer2 overexpression is associated with an aggressive form of breast cancer and malignant transformation. We sought to determine if a nano-carrier system could introduce Her2 protein to non-malignant cells and determine the effects on cell phenotype and transcriptome. With stimulation with Her2-NLPs, we observed uptake of Her2 protein and a decreased probability of individual non-malignant cells forming polar growth arrested acinar-like structures. The NLP delivery system alone or Her2-NLPs plus trastuzumab showed no effect on acinar organization rate. Transcriptomics revealed essentially no effect of empty NLPs versus untreated cells whereas Her2-NLPs versus either untreated or empty NLP treated cells revealed upregulation of several factors associated with breast cancer. Pathway analysis also suggested that known nodes downstream of Her2 were activated in response to Her2-NLP treatment. This suggests that Her2-NLPs are sufficient for malignant transformation of non-malignant cells and that this system offers a new model for studying cell surface receptor signaling without genomic modification or transformation techniques.

HER2 expression and HER2:HER2 dimerization identifies subpopulations of metastatic breast cancer patients with different probabilities of long-term survival following trastuzumab treatment and with different requirements for concomitant chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10557-10557 ◽  
Author(s):  
M. P. Bates ◽  
C. Desmedt ◽  
J. Sperinde ◽  
W. Huang ◽  
D. Larsimont ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Protein Expression ◽  
Metastatic Breast ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Concomitant Chemotherapy ◽  
Term Survival ◽  
Her2 Protein ◽  
Trastuzumab Treatment

10557 Background: Selection of patients for treatment with trastuzumab is currently based on the semi-quantitative measurement of HER2 protein expression (IHC) or gene amplification (FISH). We made quantitative measurements of HER2 expression and homodimerization using a novel assay, eTag, and correlated them with overall survival (OS) and time-to-progression (TTP) following trastuzumab treatment in a cohort of patients with metastatic breast cancer (MBC). We also examined the benefit of concomitant chemotherapy (CT) depending on quantitative HER2 expression. Methods: The Jules Bordet cohort (Brussels, Belgium, N=71) had MBC and prior treatment with at least two CT regimens. Patients received trastuzumab alone or combined with predominantly paclitaxel. Independent medical data review and central confirmation of HER2 overexpression by FISH (N=64) or IHC (N=7) were mandatory. The eTag assay was used to quantitate HER2 protein expression and HER2:HER2 dimers in FFPE specimens. eTag measurements were correlated with OS and TTP using Kaplan-Meier and Cox Proportional Hazards regression analyses. Results: Cox analyses identified three independent correlates of OS and TTP: number of metastatic sites (HROS = 2.4/site, 95%CI 1.5–3.9, p = 0.00019), treatment with trastuzumab only (HROS = 2.8, 95%CI 1.1–7.3, p = 0.036), and HER2 expression level (HROS = 0.24/log10(HER2), 95%CI 0.09–0.7, p = 0.0058). Patients with high HER2 (above median expression) experienced better OS than those with low HER2 (HR 0.24, p = 0.0014). Patients with high HER2 expression did not benefit from added CT (HR = 0.95, 95%CI 0.24–3.8, p = 0.94), while patients with low HER2 expression did (trastuzumab alone HR 4.4, 95% CI 1.3–18, p = 0.018). Similar results were observed for HER2:HER2 dimerization. Conclusions: Within a population of patients selected by FISH or IHC to receive trastuzumab, higher HER2 expression or HER2:HER2 dimerization correlated with better outcomes. Patients with high HER2 expression derived no benefit from concomitant CT, while patients with low HER2 expression benefited significantly from the addition of CT to trastuzumab. No significant financial relationships to disclose.

Impact of ErbB receptors and anticancer drugs against breast cancer: A review

2021 ◽  
Vol 22 ◽  
Author(s):  
Ankita Sahu ◽  
Saurabh Verma ◽  
Meena Varma ◽  
Manoj Kumar Yadav
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinase ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Growth Factor Receptor ◽  
Cell Surface Receptor ◽  
Erbb Receptors ◽  
Anticancer Drug Delivery ◽  
Intracellular Signaling Pathways ◽  
Surface Receptor

: Human EGFR (Epidermal Growth Factor Receptor) family of tyrosine kinase receptors consists of four members, ErbB1-4. Abnormalities in the ErbB family characterize a variety of human cancers, including breast cancer. Tyrosine kinase is recruited by the activated EGFR cell surface receptor, which transmits signals from the receptor to interact with intracellular signaling pathways and regulates cellular functions and biological processes. Targeting the intracellular signaling pathways has been aided in the drug development that was already in use and more continually being developed. This review article highlights the function of ErbB receptors/ligands, their role in signaling pathways, effective targeted drugs, and a combination of targeted drug strategies in breast cancer treatment that could lead to the novel combination of anticancer drug delivery systems.

scholarly journals Decreased nonspecific adhesivity, receptor-targeted therapeutic nanoparticles for primary and metastatic breast cancer

2020 ◽  
Vol 6 (3) ◽  
pp. eaax3931 ◽  
Author(s):  
Jimena G. Dancy ◽  
Aniket S. Wadajkar ◽  
Nina P. Connolly ◽  
Rebeca Galisteo ◽  
Heather M. Ames ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Surface ◽  
Tumor Cell ◽  
Specific Binding ◽  
Metastatic Breast ◽  
Cell Surface Receptor ◽  
Surface Receptor ◽  
Specific Uptake ◽  
Effective Development ◽  
The Brain

Development of effective tumor cell–targeted nanodrug formulations has been quite challenging, as many nanocarriers and targeting moieties exhibit nonspecific binding to cellular, extracellular, and intravascular components. We have developed a therapeutic nanoparticle formulation approach that balances cell surface receptor-specific binding affinity while maintaining minimal interactions with blood and tumor tissue components (termed “DART” nanoparticles), thereby improving blood circulation time, biodistribution, and tumor cell–specific uptake. Here, we report that paclitaxel (PTX)–DART nanoparticles directed to the cell surface receptor fibroblast growth factor–inducible 14 (Fn14) outperformed both the corresponding PTX-loaded, nontargeted nanoparticles and Abraxane, an FDA-approved PTX nanoformulation, in both a primary triple-negative breast cancer (TNBC) model and an intracranial model reflecting TNBC growth following metastatic dissemination to the brain. These results provide new insights into methods for effective development of therapeutic nanoparticles as well as support the continued development of the DART platform for primary and metastatic tumors.

Nanolipoprotein-Mediated Her2 Protein Transfection Induces Malignant Transformation in Human Breast Acinar Cultures

ACS Omega ◽  
2021 ◽  
Author(s):  
Wei He ◽  
Angela C. Evans ◽  
William F. Hynes ◽  
Matthew A. Coleman ◽  
Claire Robertson
Keyword(s):  
Malignant Transformation ◽  
Human Breast ◽  
Her2 Protein ◽  
Protein Transfection

scholarly journals Mitochondria-Related Core Genes in Breast Cancer: Potential Diagnostic, Prognostic Markers and Therapeutic Targets

2020 ◽  
Author(s):  
Li-rong Yan ◽  
Ang Wang ◽  
Zhi Lv ◽  
Yuan Yuan ◽  
Qian Xu
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cell Communication ◽  
Therapeutic Targets ◽  
Cell Surface Receptor ◽  
Apoptosis Pathway ◽  
Diagnosis And Prognosis ◽  
Kaplan Meier ◽  
Surface Receptor ◽  
Molecular Therapeutic

Abstract Background: Mitochondria-nuclear cross talk and mitochondrial retrograde regulation are involved in the genesis and development of breast cancer (BC). Therefore, mitochondria can be regarded as a promising target for BC therapeutic strategies. In the present study, we aimed to seek the potential biomarkers of BC diagnosis and prognosis and also the molecular therapeutic targets from the perspective of mitochondrial dysfunction.Methods: The microarray data of mitochondria-related encoding genes of BC were downloaded from GEO including GSE128610 and GSE72319. GSE128610 was treated as test set and validation sets consisted of GSE72319 and TCGA, which were used for identifying mitochondria-related differential expressed genes (mrDEGs). GO analysis and KEGG mapping of validated mrDEGs was performed by STRING and KEGG mapper, respectively. PPI network was constructed by STRING. MCODE was applied to modeling prediction of PPI and hub mrDEGs were screened by cytohubba. The online tool of Kaplan Meier plotter was adopted to analyze the correlation between hub mrDEGs and the overall survival of BC patients.Results: A total of 23 up-regulated and 71 down-regulated mrDEGs were identified and validated. Enrichment analyses indicated that mrDEGs were associated with several biological processes, including cell migration, cell surface receptor signaling pathway, cell differentiation and cell communication. Meanwhile, these genes were mapped in PI3K-ALT pathway, TGF-beta pathway, evading apoptosis pathway and resistance to chemotherapy pathway. Moreover, 9 hub mrDEGs were identified. Among them, up-regulated hub mrDEGs contained FN1, BGN, EFNA3, COL5A2 and SEMA3F, and down-regulated hub mrDEGs comprised RHOQ, SEMA3A, NRP1 and DDR2. Overall survival analysis suggested that the up-regulated FN1 and SEMA3F and down-regulated DDR2 conferred to poor BC prognosis.Conclusion: The 9 hub mrDEGs, especially FN1, SEMA3F and DDR2, were likely to regulate mitochondrial function and might be novel biomarkers of BC diagnosis and prognosis as well as the therapeutic targets.

scholarly journals Detection of Genetic Polymorphism of HER2 Gene in HER2 Positive Breast Cancer Women in Iraq

2021 ◽  
pp. 3507-3520
Author(s):  
Sahar M. Hussein ◽  
Fatimah A. Abdul Jabbar ◽  
Hadeel Mohamed Khalaf
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Subtype ◽  
Critical Role ◽  
Protein A ◽  
Control Group ◽  
Her2 Overexpression ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Her2 Protein ◽  
Iraqi Women

     The human epidermal growth factor receptor-2 (HER2) gene plays a critical role in breast cancer development and progression. HER2 overexpression characterizes a biologically and clinically aggressive breast cancer subtype. In this study, 60 samples from Iraqi women with breast cancer were collected and investigated for HER2 protein in the tissue by immunohistochemistry. Also, 20 samples from healthy Iraqi women were used as a control. The results showed that 18 (30 %) patients expressed the HER2 protein. A molecular study for single nucleotide polymorphism (SNP) was conducted on samples metastasizing to lymph nodes. DNA was extracted and polymerase chain reaction (PCR) was performed to amplify exon 17 and intron 17 of HER2 gene. Sequencing of PCR product was achieved and  two SNPs of HER2 gene, one in exon 17 (Ile655Val) and another  close to it in intron 17 (rs903506) were studied.  In exon 17, SNP Ile655Val was found in 41% of patients, while in intron 17, the non-coding SNP rs903506 was found in 27% of patients. However, no polymorphism was found in the control group. The results may suggest that HER2 gene can be used as a molecular marker for breast cancer.

scholarly journals A feed-forward loop between SorLA and HER3 determines heregulin response and neratinib resistance

Oncogene ◽  
2021 ◽  
Author(s):  
Hussein Al-Akhrass ◽  
James R. W. Conway ◽  
Annemarie Svane Aavild Poulsen ◽  
Ilkka Paatero ◽  
Jasmin Kaivola ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Xenograft Model ◽  
Mitogen Activated Protein Kinase ◽  
Cell Surface Receptor ◽  
Current Evidence ◽  
Dependent Manner ◽  
Surface Receptor ◽  
Cancer Spheroids

AbstractCurrent evidence indicates that resistance to the tyrosine kinase-type cell surface receptor (HER2)-targeted therapies is frequently associated with HER3 and active signaling via HER2-HER3 dimers, particularly in the context of breast cancer. Thus, understanding the response to HER2-HER3 signaling and the regulation of the dimer is essential to decipher therapy relapse mechanisms. Here, we investigate a bidirectional relationship between HER2-HER3 signaling and a type-1 transmembrane sorting receptor, sortilin-related receptor (SorLA; SORL1). We demonstrate that heregulin-mediated signaling supports SorLA transcription downstream of the mitogen-activated protein kinase pathway. In addition, we demonstrate that SorLA interacts directly with HER3, forming a trimeric complex with HER2 and HER3 to attenuate lysosomal degradation of the dimer in a Ras-related protein Rab4-dependent manner. In line with a role for SorLA in supporting the stability of the HER2 and HER3 receptors, loss of SorLA compromised heregulin-induced cell proliferation and sensitized metastatic anti-HER2 therapy-resistant breast cancer cells to neratinib in cancer spheroids in vitro and in vivo in a zebrafish brain xenograft model.

Expression, function, and localization of the REG cell surface receptor

2001 ◽  
Vol 120 (5) ◽  
pp. A18-A19
Author(s):  
B DIECKGRAEFE ◽  
C HOUCHEN ◽  
H ZHANG
Keyword(s):  
Cell Surface ◽  
Cell Surface Receptor ◽  
Surface Receptor
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