Related Experiment Video

Updated: Jun 25, 2026

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

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells

Published on: April 7, 2017

Expression of epidermal growth factor receptor or ErbB3 facilitates geldanamycin-induced down-regulation of ErbB2

Nina Marie Pedersen1, Kamilla Breen, Marianne Skeie Rødland

  • 1Institute of Pathology, Faculty of Medicine, University of Oslo, Oslo, Norway.

Molecular Cancer Research : MCR
|February 12, 2009
PubMed

Insights

Overexpression of epidermal growth factor receptor (EGFR) family members like ErbB2 and ErbB3 enhances cancer cell growth. Co-expression with EGFR significantly increases ErbB2 down-regulation by geldanamycin, suggesting potential therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Overexpression of epidermal growth factor receptor (EGFR), ErbB2, and ErbB3 drives cancer cell proliferation and survival.
  • ErbB2 overexpression in breast cancer correlates with poor prognosis, highlighting the need for therapeutic strategies targeting ErbB2.
  • Unlike EGFR, ErbB2 exhibits deficient endocytosis, posing challenges for its therapeutic targeting.

Purpose of the Study:

  • To investigate the effect of co-expressed EGFR and ErbB3 on the geldanamycin-induced down-regulation of ErbB2.
  • To explore the relationship between heterodimerization and the efficacy of geldanamycin derivatives in targeting ErbB2 in cancer cells.

Main Methods:

  • Utilized stably transfected isogenic cell lines expressing ErbB2 alone or in combination with EGFR and/or ErbB3.
  • Administered geldanamycin to these cell lines to assess ErbB2 down-regulation.
  • Analyzed the correlation between ErbB2 down-regulation and its activation/phosphorylation status.

Main Results:

  • Geldanamycin effectively down-regulated ErbB2 in cells expressing ErbB2 alone.
  • The rate of geldanamycin-induced ErbB2 down-regulation was significantly enhanced in cells co-expressing EGFR and/or ErbB3.
  • This enhanced down-regulation did not correlate with increased ErbB2 activation or phosphorylation.

Conclusions:

  • Co-expression of EGFR and/or ErbB3 potentiates geldanamycin-induced ErbB2 down-regulation.
  • Heterodimer formation involving ErbB2 in breast cancer cells may predict response to geldanamycin derivative therapies.
  • These findings suggest a potential therapeutic strategy for ErbB2-positive breast cancers by targeting heterodimerization pathways.

More Related Videos

A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors09:04

A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors

Published on: March 15, 2016

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

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...
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.
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
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...