Related Experiment Video

Updated: Jul 18, 2026

Development and Application of Rapamycin-regulated Tyrosine Phosphatases
06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

Epidermal growth factor receptor-induced activator protein 1 activity controls density-dependent growth inhibition in

Jorrit J Hornberg1, Henk Dekker, Peter H J Peters

  • 1Department of Molecular Cell Physiology, Faculty of Earth and Life Sciences, Vrije Universiteit, Amsterdam, the Netherlands. jorrit.hornberg@organon.com

Molecular Biotechnology
|December 19, 2006
PubMed

Insights

Density-dependent growth inhibition in fibroblasts relies on epidermal growth factor (EGF) receptor levels. Declining EGF receptor expression in confluent cells impairs growth control, potentially contributing to neoplasia.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Cancer research

Background:

  • Tissue homeostasis relies on density-dependent growth inhibition.
  • Dysregulation of growth control mechanisms contributes to neoplasia.
  • Confluent normal rat kidney (NRK) fibroblasts show reduced epidermal growth factor (EGF) receptor levels, leading to EGF unresponsiveness.

Purpose of the Study:

  • To investigate the role of the EGF receptor in density-dependent growth control in NRK fibroblasts.
  • To understand the signaling pathways involved in growth arrest and restoration.

Main Methods:

  • Utilized an activator protein (AP)-1 sensitive reporter construct to measure AP-1 activity.
  • Assessed the effect of cell density, EGF treatment, and retinoic acid pretreatment on NRK fibroblasts.
  • Monitored S-phase entry as an indicator of mitogenic signaling.

Main Results:

  • AP-1 activity was significantly decreased in density-arrested NRK cells.
  • AP-1 activity was restored upon relaxation of density-dependent growth inhibition.
  • EGF failed to induce AP-1 activity or S-phase entry in density-arrested cells.
  • Retinoic acid pretreatment enhanced EGF receptor expression and restored EGF-induced AP-1 activity and S-phase entry.

Conclusions:

  • The EGF receptor plays a crucial role in regulating density-dependent growth control in NRK fibroblasts.
  • EGF-induced mitogenic signaling and AP-1 activity are key components of this regulatory process.
  • Restoring EGF receptor expression can overcome density-dependent growth arrest.

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

Intravascular Delivery of Biologics to the Rat Kidney07:29

Intravascular Delivery of Biologics to the Rat Kidney

Published on: September 1, 2016

Related Concept Videos

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...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...