Related Experiment Video

Updated: Aug 13, 2026

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
11:42

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells

Published on: April 7, 2017

Enhanced tumorigenesis of NR6 cells which express non-down-regulating epidermal growth factor receptors

H Masui1, A Wells, C S Lazar

  • 1Memorial Sloan Kettering Institute, New York, New York 10021.

Cancer Research
|November 15, 1991
PubMed

Insights

Defective epidermal growth factor (EGF) receptor down-regulation leads to rapid tumor growth. Non-down-regulating EGF receptors promote excessive signaling and enhanced tumor formation in mice.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Epidermal Growth Factor (EGF) receptor signaling is crucial for cell growth and proliferation.
  • Receptor down-regulation, a process involving internalization and degradation, normally limits excessive signaling.
  • Defects in EGF receptor internalization and down-regulation are implicated in uncontrolled cell growth.

Purpose of the Study:

  • To investigate the role of EGF receptor down-regulation in attenuating mitogenic signals.
  • To determine if impaired EGF receptor down-regulation contributes to tumor formation.
  • To compare the tumorigenic potential of cells expressing wild-type versus mutant EGF receptors.

Main Methods:

  • Utilized NR6 cells expressing either holo (wild-type) or mutant, down-regulation-defective EGF receptors.
  • Assessed tumor formation in athymic mice as a measure of tumorigenic potential.
  • Analyzed tumor growth rates and receptor expression levels after serial passage.
  • Investigated the effect of an anti-EGF receptor monoclonal antibody on tumor growth.

Main Results:

  • NR6 cells expressing mutant EGF receptors formed rapidly growing tumors.
  • Cells with holo EGF receptors exhibited low tumorigenic potential.
  • Tumor formation rate correlated with increased expression of mutant EGF receptors.
  • Tumor growth was significantly inhibited by an anti-EGF receptor antibody.

Conclusions:

  • Sequences in the EGF receptor's carboxyl terminus are essential for ligand-induced internalization and down-regulation.
  • Non-down-regulating EGF receptors provide a strong growth signal, leading to rapid tumor growth.
  • Impaired EGF receptor down-regulation is a mechanism contributing to excessive signaling and enhanced tumorigenesis.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
Renewal of Skin Epidermal Stem Cells01:12

Renewal of Skin Epidermal Stem Cells

The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular cells,...
Clinical Applications of Epidermal Stem Cells01:19

Clinical Applications of Epidermal Stem Cells

Epidermal stem cells (EpiSCs) are mainly located at the basal layer of the epidermis. These cells repair minor injuries of the skin and replace dead skin cells. However, EpiSCs’ cannot heal severe wounds such as major burns or those from diabetes or hereditary disorders. In such cases, culturing the epidermal stem cells from the patient is possible and has yielded successful treatment options, such as laboratory-grown skin grafts. These grafts are synthesized using a patient’s own EpiSCs...