Runx3 is a crucial regulator of alveolar differentiation and lung tumorigenesis in mice

Jong Min Lee, Jeong Oh Shin, Kyoung Won Cho, Akihiro Hosoya, Sung Won Cho, You Soub Lee, Hyun Mo Ryoo, Suk Chul Bae, Hansung Jung

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The runt-domain transcription factor Runx3 plays crucial roles during development such as regulating gene expression. It has been shown that Runx3 is involved in neurogenesis, thymopoiesis and functions like a tumor suppressor. Runx3 null mouse die soon after birth as a result of multiple organ defects. Runx3 null mouse lung shows an abnormal phenotype and loss of Runx3 induced remodeling in the lung. Interestingly, lung adenocarcinoma is observed in Runx3 heterozygous mice at 18 months of age. During lung development various cellular and molecular events occur such as cell proliferation, cell death, differentiation and epithelial-mesenchymal transition (EMT). To understand the specific lethal events in Runx3 null mice, we examined cellular and molecular networks involved in EMT, and EMT inducers were quantified by RT-qPCR during lung development. Excessive EMT was observed in lungs at PN1 day in Runx3 null mice and PN18 months in Runx3 heterozygous mice. Pharmacologic inhibition of EMT was used to curb tumor progression. In this study, U0126 was injected to pregnant mouse for inhibition of pERK signaling. After U0126 treatment, life spans of newborn mice were increased and lung hyperplasia was partially rescued by down-regulated cell proliferation and EMT. Our data suggest that Runx3 is involved in crucial regulation of alveolar differentiation and tumor suppression in developing mouse lung.

Original languageEnglish
Pages (from-to)261-268
Number of pages8
JournalDifferentiation
Volume81
Issue number4
DOIs
Publication statusPublished - 2011 Apr 1

Fingerprint

Carcinogenesis
Epithelial-Mesenchymal Transition
Lung
Core Binding Factor alpha Subunits
Cell Proliferation
Neoplasms
Neurogenesis
Hyperplasia
Cell Differentiation
Cell Death
Transcription Factors
Parturition
Phenotype
Gene Expression

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology
  • Cancer Research

Cite this

Lee, Jong Min ; Shin, Jeong Oh ; Cho, Kyoung Won ; Hosoya, Akihiro ; Cho, Sung Won ; Lee, You Soub ; Ryoo, Hyun Mo ; Bae, Suk Chul ; Jung, Hansung. / Runx3 is a crucial regulator of alveolar differentiation and lung tumorigenesis in mice. In: Differentiation. 2011 ; Vol. 81, No. 4. pp. 261-268.
@article{7bb9843faed0428a8b37e65a2312c1eb,
title = "Runx3 is a crucial regulator of alveolar differentiation and lung tumorigenesis in mice",
abstract = "The runt-domain transcription factor Runx3 plays crucial roles during development such as regulating gene expression. It has been shown that Runx3 is involved in neurogenesis, thymopoiesis and functions like a tumor suppressor. Runx3 null mouse die soon after birth as a result of multiple organ defects. Runx3 null mouse lung shows an abnormal phenotype and loss of Runx3 induced remodeling in the lung. Interestingly, lung adenocarcinoma is observed in Runx3 heterozygous mice at 18 months of age. During lung development various cellular and molecular events occur such as cell proliferation, cell death, differentiation and epithelial-mesenchymal transition (EMT). To understand the specific lethal events in Runx3 null mice, we examined cellular and molecular networks involved in EMT, and EMT inducers were quantified by RT-qPCR during lung development. Excessive EMT was observed in lungs at PN1 day in Runx3 null mice and PN18 months in Runx3 heterozygous mice. Pharmacologic inhibition of EMT was used to curb tumor progression. In this study, U0126 was injected to pregnant mouse for inhibition of pERK signaling. After U0126 treatment, life spans of newborn mice were increased and lung hyperplasia was partially rescued by down-regulated cell proliferation and EMT. Our data suggest that Runx3 is involved in crucial regulation of alveolar differentiation and tumor suppression in developing mouse lung.",
author = "Lee, {Jong Min} and Shin, {Jeong Oh} and Cho, {Kyoung Won} and Akihiro Hosoya and Cho, {Sung Won} and Lee, {You Soub} and Ryoo, {Hyun Mo} and Bae, {Suk Chul} and Hansung Jung",
year = "2011",
month = "4",
day = "1",
doi = "10.1016/j.diff.2011.02.001",
language = "English",
volume = "81",
pages = "261--268",
journal = "Differentiation",
issn = "0301-4681",
publisher = "Elsevier BV",
number = "4",

}

Lee, JM, Shin, JO, Cho, KW, Hosoya, A, Cho, SW, Lee, YS, Ryoo, HM, Bae, SC & Jung, H 2011, 'Runx3 is a crucial regulator of alveolar differentiation and lung tumorigenesis in mice', Differentiation, vol. 81, no. 4, pp. 261-268. https://doi.org/10.1016/j.diff.2011.02.001

Runx3 is a crucial regulator of alveolar differentiation and lung tumorigenesis in mice. / Lee, Jong Min; Shin, Jeong Oh; Cho, Kyoung Won; Hosoya, Akihiro; Cho, Sung Won; Lee, You Soub; Ryoo, Hyun Mo; Bae, Suk Chul; Jung, Hansung.

In: Differentiation, Vol. 81, No. 4, 01.04.2011, p. 261-268.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Runx3 is a crucial regulator of alveolar differentiation and lung tumorigenesis in mice

AU - Lee, Jong Min

AU - Shin, Jeong Oh

AU - Cho, Kyoung Won

AU - Hosoya, Akihiro

AU - Cho, Sung Won

AU - Lee, You Soub

AU - Ryoo, Hyun Mo

AU - Bae, Suk Chul

AU - Jung, Hansung

PY - 2011/4/1

Y1 - 2011/4/1

N2 - The runt-domain transcription factor Runx3 plays crucial roles during development such as regulating gene expression. It has been shown that Runx3 is involved in neurogenesis, thymopoiesis and functions like a tumor suppressor. Runx3 null mouse die soon after birth as a result of multiple organ defects. Runx3 null mouse lung shows an abnormal phenotype and loss of Runx3 induced remodeling in the lung. Interestingly, lung adenocarcinoma is observed in Runx3 heterozygous mice at 18 months of age. During lung development various cellular and molecular events occur such as cell proliferation, cell death, differentiation and epithelial-mesenchymal transition (EMT). To understand the specific lethal events in Runx3 null mice, we examined cellular and molecular networks involved in EMT, and EMT inducers were quantified by RT-qPCR during lung development. Excessive EMT was observed in lungs at PN1 day in Runx3 null mice and PN18 months in Runx3 heterozygous mice. Pharmacologic inhibition of EMT was used to curb tumor progression. In this study, U0126 was injected to pregnant mouse for inhibition of pERK signaling. After U0126 treatment, life spans of newborn mice were increased and lung hyperplasia was partially rescued by down-regulated cell proliferation and EMT. Our data suggest that Runx3 is involved in crucial regulation of alveolar differentiation and tumor suppression in developing mouse lung.

AB - The runt-domain transcription factor Runx3 plays crucial roles during development such as regulating gene expression. It has been shown that Runx3 is involved in neurogenesis, thymopoiesis and functions like a tumor suppressor. Runx3 null mouse die soon after birth as a result of multiple organ defects. Runx3 null mouse lung shows an abnormal phenotype and loss of Runx3 induced remodeling in the lung. Interestingly, lung adenocarcinoma is observed in Runx3 heterozygous mice at 18 months of age. During lung development various cellular and molecular events occur such as cell proliferation, cell death, differentiation and epithelial-mesenchymal transition (EMT). To understand the specific lethal events in Runx3 null mice, we examined cellular and molecular networks involved in EMT, and EMT inducers were quantified by RT-qPCR during lung development. Excessive EMT was observed in lungs at PN1 day in Runx3 null mice and PN18 months in Runx3 heterozygous mice. Pharmacologic inhibition of EMT was used to curb tumor progression. In this study, U0126 was injected to pregnant mouse for inhibition of pERK signaling. After U0126 treatment, life spans of newborn mice were increased and lung hyperplasia was partially rescued by down-regulated cell proliferation and EMT. Our data suggest that Runx3 is involved in crucial regulation of alveolar differentiation and tumor suppression in developing mouse lung.

UR - http://www.scopus.com/inward/record.url?scp=79954570409&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79954570409&partnerID=8YFLogxK

U2 - 10.1016/j.diff.2011.02.001

DO - 10.1016/j.diff.2011.02.001

M3 - Article

C2 - 21367515

AN - SCOPUS:79954570409

VL - 81

SP - 261

EP - 268

JO - Differentiation

JF - Differentiation

SN - 0301-4681

IS - 4

ER -