Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer

K. S. Lee, Y. S. Lee, J. M. Lee, K. Ito, S. Cinghu, J. H. Kim, J. W. Jang, Y. H. Li, Y. M. Goh, X. Z. Chi, H. Wee, Han Woong Lee, A. Hosoya, J. H. Chung, J. J. Jang, J. K. Kundu, Y. J. Surh, W. J. Kim, Y. Ito, Hansung Jung & 1 others S. C. Bae

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Human lung adenocarcinoma, the most prevalent form of lung cancer, is characterized by many molecular abnormalities. K-ras mutations are associated with the initiation of lung adenocarcinomas, but K-ras-independent mechanisms may also initiate lung tumors. Here, we find that the runt-related transcription factor Runx3 is essential for normal murine lung development and is a tumor suppressor that prevents lung adenocarcinoma. Runx3-/-mice, which die soon after birth, exhibit alveolar hyperplasia. Importantly, Runx3-/-bronchioli exhibit impaired differentiation, as evidenced by the accumulation of epithelial cells containing specific markers for both alveolar (that is SP-B) and bronchiolar (that is CC10) lineages. Runx3+-/-epithelial cells also express Bmi1, which supports self-renewal of stem cells. Lung adenomas spontaneously develop in aging Runx3+-/-mice (B18 months after birth) and invariably exhibit reduced levels of Runx3. As K-ras mutations are very rare in these adenomas, Run3+-/-mice provide an animal model for lung tumorigenesis that recapitulates the preneoplastic stage of human lung adenocarcinoma development, which is independent of K-Ras mutation. We conclude that Runx3 is essential for lung epithelial cell differentiation, and that downregulation of Runx3 is causally linked to the preneoplastic stage of lung adenocarcinoma.

Original languageEnglish
Pages (from-to)3349-3361
Number of pages13
JournalOncogene
Volume29
Issue number23
DOIs
Publication statusPublished - 2010 Jun 10

Fingerprint

Lung Neoplasms
Epithelial Cells
Lung
Adenoma
Mutation
Parturition
Hyperplasia
Cell Differentiation
Neoplasms
Carcinogenesis
Transcription Factors
Down-Regulation
Animal Models
Adenocarcinoma of lung

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Lee, K. S., Lee, Y. S., Lee, J. M., Ito, K., Cinghu, S., Kim, J. H., ... Bae, S. C. (2010). Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer. Oncogene, 29(23), 3349-3361. https://doi.org/10.1038/onc.2010.79
Lee, K. S. ; Lee, Y. S. ; Lee, J. M. ; Ito, K. ; Cinghu, S. ; Kim, J. H. ; Jang, J. W. ; Li, Y. H. ; Goh, Y. M. ; Chi, X. Z. ; Wee, H. ; Lee, Han Woong ; Hosoya, A. ; Chung, J. H. ; Jang, J. J. ; Kundu, J. K. ; Surh, Y. J. ; Kim, W. J. ; Ito, Y. ; Jung, Hansung ; Bae, S. C. / Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer. In: Oncogene. 2010 ; Vol. 29, No. 23. pp. 3349-3361.
@article{9ed582a3fa65477ab1df5bc4b8f27f4c,
title = "Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer",
abstract = "Human lung adenocarcinoma, the most prevalent form of lung cancer, is characterized by many molecular abnormalities. K-ras mutations are associated with the initiation of lung adenocarcinomas, but K-ras-independent mechanisms may also initiate lung tumors. Here, we find that the runt-related transcription factor Runx3 is essential for normal murine lung development and is a tumor suppressor that prevents lung adenocarcinoma. Runx3-/-mice, which die soon after birth, exhibit alveolar hyperplasia. Importantly, Runx3-/-bronchioli exhibit impaired differentiation, as evidenced by the accumulation of epithelial cells containing specific markers for both alveolar (that is SP-B) and bronchiolar (that is CC10) lineages. Runx3+-/-epithelial cells also express Bmi1, which supports self-renewal of stem cells. Lung adenomas spontaneously develop in aging Runx3+-/-mice (B18 months after birth) and invariably exhibit reduced levels of Runx3. As K-ras mutations are very rare in these adenomas, Run3+-/-mice provide an animal model for lung tumorigenesis that recapitulates the preneoplastic stage of human lung adenocarcinoma development, which is independent of K-Ras mutation. We conclude that Runx3 is essential for lung epithelial cell differentiation, and that downregulation of Runx3 is causally linked to the preneoplastic stage of lung adenocarcinoma.",
author = "Lee, {K. S.} and Lee, {Y. S.} and Lee, {J. M.} and K. Ito and S. Cinghu and Kim, {J. H.} and Jang, {J. W.} and Li, {Y. H.} and Goh, {Y. M.} and Chi, {X. Z.} and H. Wee and Lee, {Han Woong} and A. Hosoya and Chung, {J. H.} and Jang, {J. J.} and Kundu, {J. K.} and Surh, {Y. J.} and Kim, {W. J.} and Y. Ito and Hansung Jung and Bae, {S. C.}",
year = "2010",
month = "6",
day = "10",
doi = "10.1038/onc.2010.79",
language = "English",
volume = "29",
pages = "3349--3361",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "23",

}

Lee, KS, Lee, YS, Lee, JM, Ito, K, Cinghu, S, Kim, JH, Jang, JW, Li, YH, Goh, YM, Chi, XZ, Wee, H, Lee, HW, Hosoya, A, Chung, JH, Jang, JJ, Kundu, JK, Surh, YJ, Kim, WJ, Ito, Y, Jung, H & Bae, SC 2010, 'Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer', Oncogene, vol. 29, no. 23, pp. 3349-3361. https://doi.org/10.1038/onc.2010.79

Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer. / Lee, K. S.; Lee, Y. S.; Lee, J. M.; Ito, K.; Cinghu, S.; Kim, J. H.; Jang, J. W.; Li, Y. H.; Goh, Y. M.; Chi, X. Z.; Wee, H.; Lee, Han Woong; Hosoya, A.; Chung, J. H.; Jang, J. J.; Kundu, J. K.; Surh, Y. J.; Kim, W. J.; Ito, Y.; Jung, Hansung; Bae, S. C.

In: Oncogene, Vol. 29, No. 23, 10.06.2010, p. 3349-3361.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer

AU - Lee, K. S.

AU - Lee, Y. S.

AU - Lee, J. M.

AU - Ito, K.

AU - Cinghu, S.

AU - Kim, J. H.

AU - Jang, J. W.

AU - Li, Y. H.

AU - Goh, Y. M.

AU - Chi, X. Z.

AU - Wee, H.

AU - Lee, Han Woong

AU - Hosoya, A.

AU - Chung, J. H.

AU - Jang, J. J.

AU - Kundu, J. K.

AU - Surh, Y. J.

AU - Kim, W. J.

AU - Ito, Y.

AU - Jung, Hansung

AU - Bae, S. C.

PY - 2010/6/10

Y1 - 2010/6/10

N2 - Human lung adenocarcinoma, the most prevalent form of lung cancer, is characterized by many molecular abnormalities. K-ras mutations are associated with the initiation of lung adenocarcinomas, but K-ras-independent mechanisms may also initiate lung tumors. Here, we find that the runt-related transcription factor Runx3 is essential for normal murine lung development and is a tumor suppressor that prevents lung adenocarcinoma. Runx3-/-mice, which die soon after birth, exhibit alveolar hyperplasia. Importantly, Runx3-/-bronchioli exhibit impaired differentiation, as evidenced by the accumulation of epithelial cells containing specific markers for both alveolar (that is SP-B) and bronchiolar (that is CC10) lineages. Runx3+-/-epithelial cells also express Bmi1, which supports self-renewal of stem cells. Lung adenomas spontaneously develop in aging Runx3+-/-mice (B18 months after birth) and invariably exhibit reduced levels of Runx3. As K-ras mutations are very rare in these adenomas, Run3+-/-mice provide an animal model for lung tumorigenesis that recapitulates the preneoplastic stage of human lung adenocarcinoma development, which is independent of K-Ras mutation. We conclude that Runx3 is essential for lung epithelial cell differentiation, and that downregulation of Runx3 is causally linked to the preneoplastic stage of lung adenocarcinoma.

AB - Human lung adenocarcinoma, the most prevalent form of lung cancer, is characterized by many molecular abnormalities. K-ras mutations are associated with the initiation of lung adenocarcinomas, but K-ras-independent mechanisms may also initiate lung tumors. Here, we find that the runt-related transcription factor Runx3 is essential for normal murine lung development and is a tumor suppressor that prevents lung adenocarcinoma. Runx3-/-mice, which die soon after birth, exhibit alveolar hyperplasia. Importantly, Runx3-/-bronchioli exhibit impaired differentiation, as evidenced by the accumulation of epithelial cells containing specific markers for both alveolar (that is SP-B) and bronchiolar (that is CC10) lineages. Runx3+-/-epithelial cells also express Bmi1, which supports self-renewal of stem cells. Lung adenomas spontaneously develop in aging Runx3+-/-mice (B18 months after birth) and invariably exhibit reduced levels of Runx3. As K-ras mutations are very rare in these adenomas, Run3+-/-mice provide an animal model for lung tumorigenesis that recapitulates the preneoplastic stage of human lung adenocarcinoma development, which is independent of K-Ras mutation. We conclude that Runx3 is essential for lung epithelial cell differentiation, and that downregulation of Runx3 is causally linked to the preneoplastic stage of lung adenocarcinoma.

UR - http://www.scopus.com/inward/record.url?scp=77953480629&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953480629&partnerID=8YFLogxK

U2 - 10.1038/onc.2010.79

DO - 10.1038/onc.2010.79

M3 - Article

VL - 29

SP - 3349

EP - 3361

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 23

ER -