Related Experiment Video

Updated: May 12, 2026

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

Nrf2 prevents initiation but accelerates progression through the Kras signaling pathway during lung carcinogenesis

Hironori Satoh1, Takashi Moriguchi, Jun Takai

  • 1Department of Medical Biochemistry and Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

Cancer Research
|April 24, 2013
PubMed

Insights

Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a dual role in lung carcinogenesis, initially preventing tumors but later promoting their malignant progression. Nrf2 inhibitors may prevent cancer advancement.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Defense Mechanisms

Background:

  • Nuclear factor erythroid 2-related factor 2 (Nrf2) is crucial for cellular defense against oxidative stress and chemical carcinogenesis.
  • Elevated NRF2 protein levels in many cancers prompt investigation into its complex role in tumorigenesis.

Purpose of the Study:

  • To elucidate the dual role of Nrf2 in lung carcinogenesis using a urethane-induced mouse model.
  • To determine how Nrf2 influences tumor initiation and malignant progression.

Main Methods:

  • Utilized a urethane-induced multistep model of lung carcinogenesis in mice.
  • Compared tumor development and characteristics in Nrf2-deficient (Nrf2(-/-)) and wild-type (Nrf2(+/+)) mice.
  • Analyzed Kras mutations in tumors from both genotypes.

Main Results:

  • Nrf2(-/-) mice showed increased tumor foci early on but fewer malignant tumors later.
  • Nrf2(+/+) tumors frequently had activated Kras mutations, unlike Nrf2(-/-) tumors.
  • Nrf2 exhibits a dual role: preventive in initiation and promoting in malignant progression.

Conclusions:

  • Nrf2 has opposing roles in lung cancer development, acting as a tumor suppressor initially and a tumor promoter later.
  • Nrf2 inhibitors are potential therapeutic agents to prevent malignant progression in lung cancer.
  • Nrf2 activators may be beneficial for lung cancer prevention strategies.

Related Concept Videos

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...
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...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
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...
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...
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: