Related Experiment Video

Updated: Jul 15, 2026

Evaluation of Keratinocyte Proliferation on Two- and Three-dimensional Type I Collagen Substrates
08:19

Evaluation of Keratinocyte Proliferation on Two- and Three-dimensional Type I Collagen Substrates

Published on: April 22, 2019

Arsenite and insulin exhibit opposing effects on epidermal growth factor receptor and keratinocyte proliferative

Timothy J Patterson1, Robert H Rice

  • 1Department of Environmental Toxicology, University of California, One Shields Avenue, Davis, CA 95616-8588, USA.

Toxicology and Applied Pharmacology
|April 3, 2007
PubMed

Insights

Arsenic exposure and epidermal growth factor (EGF) promote skin cell proliferation by maintaining EGF receptor function and activating beta-catenin signaling. This molecular mechanism may underlie arsenic

Area of Science:

  • Dermatology
  • Molecular Biology
  • Toxicology

Background:

  • Arsenic exposure is linked to skin cancer, potentially by affecting epidermal stem cell differentiation.
  • Understanding the molecular mechanisms of arsenic's action on keratinocytes is crucial for cancer prevention.

Purpose of the Study:

  • To investigate the molecular basis of how arsenite influences human epidermal keratinocyte responses to epidermal growth factor (EGF).
  • To elucidate the role of EGF receptor signaling and beta-catenin in arsenite-induced keratinocyte proliferation.

Main Methods:

  • Cultured human epidermal keratinocytes were treated with arsenite and/or EGF.
  • EGF receptor protein levels, phosphorylation, and downstream signaling pathways (beta-catenin) were analyzed.
  • Colony-forming ability and stem cell yield were assessed.

Main Results:

  • Arsenite and EGF additively preserved keratinocyte colony-forming ability, dependent on EGF receptor tyrosine kinase activity.
  • Arsenite maintained EGF receptor protein levels and phosphorylation, preserving signaling capacity.
  • Nuclear beta-catenin levels and activity increased, correlating with enhanced colony formation and stem cell yield.
  • Trivalent antimony mimicked arsenite's effects.
  • Insulin-induced loss of EGF receptor protein was prevented by arsenite.

Conclusions:

  • Arsenite and EGF cooperate to enhance keratinocyte proliferation and stem cell potential via sustained EGF receptor signaling and beta-catenin activation.
  • This mechanism provides insight into arsenic-induced skin carcinogenesis.
  • Arsenite may protect EGF receptor function against inhibitory factors like insulin.

More Related Videos

A Novel In Vitro Wound Healing Assay to Evaluate Cell Migration08:55

A Novel In Vitro Wound Healing Assay to Evaluate Cell Migration

Published on: March 17, 2018

Epigenetic Conversion as a Safe and Simple Method to Obtain Insulin-secreting Cells from Adult Skin Fibroblasts08:45

Epigenetic Conversion as a Safe and Simple Method to Obtain Insulin-secreting Cells from Adult Skin Fibroblasts

Published on: March 18, 2016

Related Concept Videos

Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...
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...
Target Cell Response to Hormones01:22

Target Cell Response to Hormones

Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
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...
Hormones Regulating Blood Glucose01:16

Hormones Regulating Blood Glucose

Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are co-secreted in...