Target HER four in breast cancer?

Brockhoff, Gero

doi:10.18632/oncotarget.26867

Cited by 10 publications

(7 citation statements)

References 31 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro studies in this cell line reported therapy resistance development to trastuzumab upon EGFR overexpression [17]. HER4 is a further candidate for forming heterodimers with other members of the HER family but the role HER4 plays in the course of breast cancer has long been unclear [18,19].…”

Section: Introductionmentioning

confidence: 99%

EGFR Expression in HER2-Driven Breast Cancer Cells

Weinberg

Peckys

Jonge

2020

IJMS

View full text Add to dashboard Cite

The epidermal growth factor receptor HER2 is overexpressed in 20% of breast cancer cases. HER2 is an orphan receptor that is activated ligand-independently by homodimerization. In addition, HER2 is able to heterodimerize with EGFR, HER3, and HER4. Heterodimerization has been proposed as a mechanism of resistance to therapy for HER2 overexpressing breast cancer. Here, a method is presented for the simultaneous detection of individual EGFR and HER2 receptors in the plasma membrane of breast cancer cells via specific labeling with quantum dot nanoparticles (QDs). Correlative fluorescence microscopy and liquid phase electron microscopy were used to analyze the plasma membrane expression levels of both receptors in individual intact cells. Fluorescent single-cell analysis of SKBR3 breast cancer cells dual-labeled for EGFR and HER2 revealed a heterogeneous expression for receptors within both the cell population as well as within individual cells. Subsequent electron microscopy of individual cells allowed the determination of individual receptors label distributions. QD-labeled EGFR was observed with a surface density of (0.5–5) × 101 QDs/µm2, whereas labeled HER2 expression was higher ranging from (2–10) × 102 QDs/µm2. Although most SKBR3 cells expressed low levels of EGFR, an enrichment was observed at large plasma membrane protrusions, and amongst a newly discovered cellular subpopulation termed EGFR-enriched cells.

show abstract

Section: Introductionmentioning

confidence: 99%

EGFR Expression in HER2-Driven Breast Cancer Cells

Weinberg

Peckys

Jonge

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…On the other hand, ERBB4 functions to counteract the oncogenic activities of ERBB2 . It has been linked to the resistance to tamoxifen treatment and is associated with the stimulation of cancer cell proliferation [ 31 ]. Mutations in these two genes might be precursors of malignant transformation considering that they are frequently mutated in the case of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

The carcinogenic capacity of arsenic in normal epithelial breast cells and double-positive breast cancer cells

Zimta,

Cenariu,

Tigu

et al. 2024

Medicine and Pharmacy Reports

View full text Add to dashboard Cite

Background and aims. The carcinogenic effect of arsenic is a subject of controversy in relation to breast cancer. In our current research, we aimed to simulate the effects of chronic low-level arsenic exposure on breast cells by intoxicating MCF-10A and MCF-7 cells with 1 μM Arsenic trioxide (As2O3) for 3 weeks (3w) and 6 weeks (6w), respectively. Methods. We assessed the cellular responses to As2O3 through various assays, including confocal fluorescence microscopy, flow cytometry for cell cycle analysis, Transwell invasion assay, scratch assay, and colony assay. Additionally, we analyzed the mutation burden in all the exposed cells by using the next generation sequencing technology. Results. Our findings indicate that As2O3 has a minor carcinogenic effect in normal cells, with no definitive evidence of malignant transformation observed after 6 weeks of exposure. In the case of breast cancer cells, As2O3 exhibits a dual effect, both inhibitory and stimulatory. It leads to reduced colony formation ability at 6 weeks, while enhancing the cells’ ability for invasion. The mutations triggered by As2O3 exposure are distributed across genes with both tumor-suppressive and oncogenic functions. Five mutations are common to both cell lines, involving the following genes: Kinase Insert Domain Receptor (KDR) (c.798+54G>A), Colony Stimulating Factor 1 Receptor (CSF1R) (c.*37AC>C, c.*35C>TC), SWI/SNF-Related Matrix-Associated Actin-Dependent Regulator of Chromatin Subfamily B Member 1 (SMARCB1) (c.1119-41C>T), and Fms-like Tyrosine Kinase 3 (FLT3) (c.1310-3T>C). Additionally, Human Epidermal Growth Factor Receptor 4 (ERBB4/HER4) (c.421+58A>G) and Human Epidermal Growth Factor Receptor 2 (HER2/ERBB2) (c.2307+46A>G) mutations were exclusively found in MCF-10A cells exposed to As2O3. Furthermore, MCF-7 cells exhibited unique mutations in the KIT Proto-Oncogene (KIT) (c.1594G>A) and TP53 (c.215C>G). Conclusion. In summary, our study reveals that a 6-weeks exposure to arsenic has a limited carcinogenic effect in normal breast cells and a dual role in breast cancer cells.

show abstract

“…We have shown that ER/HER4 double positive ZR-75-1 BC cells were basically sensitive to TAM treatment, however, the treatment efficiency, represented by a reduced cell cycle progress and an increased fraction of quiescent (i.e., not cycling) cells could be considerably enhanced by a HER4 receptor knock-down [83]. Based on additional functional studies, by which 4ICD has been identified to operate as ER-coactivator [82,84,85], we assumed that a nuclear 4ICD and ER complex / interaction impairs the inhibitory effect of TAM, while the HER4 knock-down disables this interaction and thus raises the treatment efficiency [86]. We complemented the experimental evidence by quantitative analysis of HER4 expression in 258 BC specimens and identified a poor course and outcome of premenopausal and TAM treated BC patients with HER4-positive tumor tissues, whereas TAMtreated patients with low or absent tumor-associated HER4 expression performed significantly better.…”

Section: Intracellular Activities Of Her4 In Luminal Bc -The Subcellu...mentioning

confidence: 99%