Related Experiment Video

Updated: Aug 4, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

ErbB-2 kinase is required for constitutive stat 3 activation in malignant human lung epithelial cells

A Fernandes1, A W Hamburger, B I Gerwin

  • 1Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA.

International Journal of Cancer
|October 3, 1999
PubMed

Insights

Constitutive activation of STAT 3 in non-small-cell lung cancer cells requires ErbB-2 (human epidermal growth factor receptor 2) kinase activity. This activation is driven by an autocrine loop involving ErbB-1 (epidermal growth factor receptor) and TGF-alpha.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Overexpression of ErbB-2 (human epidermal growth factor receptor 2) is linked to non-small-cell lung cancer.
  • Previous work showed c-erbB-2 transformation requires ErbB-1 (epidermal growth factor receptor) and autocrine TGF-alpha.

Purpose of the Study:

  • To investigate the role of STAT 3 activation in c-erbB-2-transformed lung epithelial cells.
  • To elucidate the mechanism of STAT 3 activation involving ErbB-1, ErbB-2, and TGF-alpha.

Main Methods:

  • Mobility shift assays and nuclear localization studies to confirm STAT 3 activation.
  • Inhibition of ErbB-2 kinase activity using tyrphostin AG825.
  • Cellular transformation assays involving human lung epithelial cells.

Main Results:

  • STAT 3 was constitutively activated in c-erbB-2-transformed cells.
  • Activation of STAT 3 was mediated by a TGF-alpha-stimulated ErbB-1/ErbB-2 heterodimer complex.
  • ErbB-1 was necessary but not sufficient for TGF-alpha-induced STAT activation.
  • Inhibition of ErbB-2 kinase activity blocked constitutive STAT 3 activation.

Conclusions:

  • ErbB-2 kinase activity is essential for constitutive STAT 3 activation.
  • An autocrine loop involving ErbB-1 and TGF-alpha establishes STAT 3 activation.
  • These findings highlight a critical signaling pathway in non-small-cell lung cancer development.

More Related Videos

Differentiation of Mouse Breast Epithelial HC11 and EpH4 Cells09:32

Differentiation of Mouse Breast Epithelial HC11 and EpH4 Cells

Published on: February 27, 2020

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

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...
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...
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...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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...