Omar Bennett
The epidermal growth factor receptor (EGFR) is a protein that plays a critical role in various biological processes, including cell growth, proliferation, and migration. Alterations in EGFR activity have been implicated in the development and progression of certain cancers, including breast cancer. MDA-MB-231 is a well-studied human breast cancer cell line that exhibits high expression levels of EGFR and has been extensively utilized in research to enhance our understanding of EGFR-mediated processes in cancer. While the specific question of whether EGFR is constitutively active in MDA-MB-231 cells requires in-depth experimental investigation, existing studies provide insights into the role of EGFR in this context.
| Characteristics | Values |
|---|---|
| EGFR levels | Predict a poor outcome in human breast cancer |
| EGFR expression | Confirmed by Western blot analysis |
| EGF | Influences human breast cancer progression via migratory pathways |
| EGF concentration | Gradients of 0.15 to 1.5 nM/mm induce directional migration |
| EGF chemotactic effects | Could not be observed in standard growth medium |
| EGF-stimulated migration | Not altered by inhibition of ERK1 and ERK2 |
| EGF-stimulated migration | Not influenced by MAP kinase |
| EGFR-mediated migration | Critical for fibroblasts |
| EGFR antagonists | Block MDA-MB-231 chemotaxis |
| EGFR antisense RNA | Blocks expression of the epidermal growth factor receptor |
| EGFR antisense RNA | Partially reverses the malignant phenotype of MDA-MB-231 cells |
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What You'll Learn
EGFR expression in MDA-MB-231 cells
MDA-MB-231 is a human breast cancer cell line that has been found to express EGFR. This receptor is commonly associated with tumour growth, proliferation, apoptosis, and cell survival. In the context of MDA-MB-231 cells, studies have shown that while these cells express EGFR, they do not exhibit a proliferative response to EGF. This is thought to be due to an activated K-ras mutation, which results in a high constitutive migration of the cells.
The role of EGFR in MDA-MB-231 cell migration has been a key area of investigation. It has been found that MDA-MB-231 cells are able to sense EGF concentration gradients, with higher gradients inducing directional migration. This migration is mediated by MAP kinase pathways, specifically through the involvement of ERK1 and ERK2. Inhibition of these kinases has been shown to reduce the migration of MDA-MB-231 cells.
Furthermore, studies have explored the use of EGFR antagonists, such as monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs), to block EGFR-mediated effects in MDA-MB-231 cells. These inhibitors have been shown to interfere with EGFR-mediated signalling and partially reverse the malignant phenotype of the cells. Additionally, the use of EGFR antisense RNA has also been found to block EGFR expression and impact the growth ability of the cells.
The interaction between EGFR and other receptors, such as HER2, has also been studied in MDA-MB-231 cells. It has been observed that EGFR can negate the proliferative effect of oncogenic HER2 in these cells. However, no significant differences were seen in proliferation, survival, or migration between MDA-MB-231 cells expressing HER2 and those that do not.
Overall, the expression of EGFR in MDA-MB-231 cells is well-established, and its role in cell migration and tumour progression is a key area of research. The understanding of EGFR expression and its functional implications in MDA-MB-231 cells has important clinical significance for the development of targeted therapies and the prevention or treatment of breast cancer.
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EGFR and cancer cell migration
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that can dimerize, auto-cross-phosphorylate, and initiate a cascade of downstream signals. It is frequently expressed in cancers and has been shown to correlate with the progression of many tumour types, including breast cancer.
EGFR levels predict a poor outcome in human breast cancer and are most commonly associated with the proliferative effects of epidermal growth factor (EGF). However, recent studies have suggested that EGF may also influence human breast cancer progression via migratory pathways, which appear to be at least partially dissociated from proliferative pathways.
MDA-MB-231 human breast cancer cells have been shown to elicit a potent chemotactic response despite their complete lack of a proliferative response to EGF. This chemotactic response is blocked by antagonists of EGFR ligation, the EGFR kinase, phosphatidylinositol 3′-kinase, and phospholipase C.
Inhibitor couples that target EGFR have been used in cancer therapy, including monoclonal antibodies (mAbs) and small-molecule tyrosine kinase inhibitors (TKIs). These inhibitors exploit the advantages of both inhibiting mechanisms while reducing the applied inhibitor doses. TKIs, in particular, are useful for inhibiting cancer cells carrying truncated forms of the receptor that are constitutively activated.
In summary, EGFR plays a critical role in cancer cell migration, and its inhibition has been shown to partially reverse the malignant phenotype of MDA-MB-231 human breast cancer cells. However, resistance to current EGFR inhibitors has been observed in some cancers, highlighting the need for further research and the development of novel therapeutic approaches.
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EGFR and chemotactic response
Chemotaxis is a process where cells migrate towards a source of chemoattractant. This process is triggered by the binding of chemoattractant molecules to cell surface receptors. The epidermal growth factor receptor (EGFR) is a chemoattractant receptor that has been linked to several vital cellular processes, including cell survival, proliferation, differentiation, and migration.
The EGFR–GFP chimera is not concentrated at the leading edges of the extending lamellipods. However, in the presence of electric fields and ligands, receptors for EGF are concentrated at the front of the cell. Chemotactic responses to EGF are increased compared to the parental cell line and are shifted to lower EGF concentrations.
MDA-MB-231 cells are able to sense EGF concentration gradients as low as 0.015 nM/mm, indicated by an increase in cell motility. Concentration gradients of 0.15 to 1.5 nM/mm were needed to induce directional migration. In order to validate EGF as a chemotactic guidance cue for MDA-MB-231, chemotaxis assays were performed in the presence of EGFR-specific inhibitors. These include monoclonal antibodies (mAbs) and small molecule tyrosine kinase inhibitors (TKIs).
EGFR antisense RNA blocks expression of the epidermal growth factor receptor and partially reverses the malignant phenotype of MDA-MB-231 cells. In vitro studies showed that the growth ability of the transfected cells was partially inhibited compared to parental cells and cells transfected with the plasmid containing the neomycin resistance gene only. It was found that EGF had an augmentation effect on the growth of transfected MDA-AS10 cells but not MDA-MB-231 cells.
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EGFR antagonists and their effects
EGFR antagonists have been shown to have a range of effects on cancer cells, particularly those associated with the MDA-MB-231 human breast cancer cell line. These antagonists can block the expression of the epidermal growth factor receptor (EGFR), which is often found at abnormally high levels in cancer cells and is associated with poor outcomes in human breast cancer.
One example of an EGFR antagonist is EGFR antisense RNA, which has been shown to partially reverse the malignant phenotype of MDA-MB-231 cells. In vitro studies have demonstrated that the growth ability of these transfected cells was partially inhibited compared to parental cells and cells transfected with a plasmid containing only the neomycin resistance gene. Flow cytometric analysis revealed an abnormal cell cycle in the transfected cells, with a decrease in the G2/M and S phases and an increase in the G1 phase, indicating a blockage in the cell cycle. Furthermore, the transfected cells showed decreased adherence to laminin and fibronectin, as well as impaired growth in soft agarose.
Another class of EGFR antagonists includes monoclonal antibodies (mAbs), which bind to the extracellular domain of EGFR and compete with endogenous ligands for the ligand-binding region, thereby blocking ligand-induced EGFR signaling. Small molecule tyrosine kinase inhibitors (TKIs) are also effective EGFR antagonists. They compete with adenosine triphosphate to bind to the intracellular catalytic tyrosine kinase domain of EGFR, inhibiting autophosphorylation and downstream signaling. TKIs are particularly useful in inhibiting cancer cells carrying truncated forms of the receptor that are constitutively activated.
The use of EGFR antagonists in cancer therapy aims to exploit the advantages of both inhibiting mechanisms while reducing the applied inhibitor doses. By targeting EGFR and interfering with its mediated effects, these antagonists can play a crucial role in blocking cancer cell migration and proliferation, which are central mechanisms during cancer cell invasion and metastasis.
Overall, EGFR antagonists have shown promising results in blocking the expression of EGFR and reversing the malignant phenotype of MDA-MB-231 human breast cancer cells. These antagonists have the potential to inhibit cancer cell growth, migration, and progression, making them valuable tools in the battle against cancer.
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EGFR and HER2 expression
EGFR antisense RNA has been shown to block the expression of the epidermal growth factor receptor and partially reverse the malignant phenotype of human breast cancer MDA-MB-231 cells. In vitro studies showed that the growth ability of the transfected cells was partially inhibited in comparison to parental cells and cells transfected with the plasmid containing the neomycin resistance gene only. Flow cytometric analysis showed that the cell cycle of the transfected cells was abnormal with a decrease of cells in the G2/M and S phases and an increase of cells in the G1 phase, indicating a blockage in phase G1.
HER2 is named for its structural similarities with human epidermal growth factor receptor 1, or HER1. HER2 is found in a variety of tumours, including non-small-cell lung cancers (NSCLC), ovarian, stomach, adenocarcinoma of the lung, and aggressive forms of uterine cancer. HER2 mutations have been found in NSCLC and can direct treatment. HER2 is the target of the monoclonal antibody trastuzumab (marketed as Herceptin), which is effective only in cancers where HER2 is overexpressed.
A dual-labelling approach has been established to simultaneously analyse the expression of individual EGFR and HER2 receptors on the surface of SKBR3 cells with correlative light and electron microscopy. This approach allows for the identification of different expression phenotypes for individual cells and for different cell surface areas on individual cells. For most cells, termed bulk, HER2 expression was enriched on the cell surface in clustered stripes or patches, with strong enrichments observed for large membrane protrusions (LMPs). Bulk cells expressed low levels of EGFR homogeneously on the cell surface, with increased EGFR expression notable at LMPs.
In summary, EGFR and HER2 expression are important biomarkers and therapeutic targets for cancer, particularly breast cancer. High EGFR levels are associated with poor outcomes in breast cancer, and EGFR antisense RNA has been shown to partially reverse the malignant phenotype of MDA-MB-231 breast cancer cells. HER2 is found in a variety of tumours and is an important therapeutic target, with trastuzumab being effective in cancers where HER2 is overexpressed. Finally, dual-labelling approaches allow for the analysis of EGFR and HER2 expression on SKBR3 cells, revealing heterogeneous expression patterns that can inform our understanding of cancer progression and treatment.
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Frequently asked questions
EGFR stands for Epidermal Growth Factor Receptor. It is a receptor commonly associated with human tumors and has been shown to correlate with the progression of many tumor types, including breast cancer.
EGFR levels predict a poor outcome in human breast cancer and are commonly associated with the proliferative effects of epidermal growth factor (EGF). MDA-MB-231 human breast cancer cells have been found to elicit a potent chemotactic response despite their complete lack of a proliferative response to EGF. This suggests that EGF may influence cancer progression in these cells via migratory pathways.
While I found information on the role of EGFR in MDA-MB-231 cells, I could not find clear information on whether it is constitutively active in these cells. However, one source mentions that mutated forms of EGFR have been identified in selected cancers where ligand-independent signaling occurs, indicating constitutive activation. Additionally, studies have shown that MDA-MB-231 cells express high levels of EGFR.
