Transforming growth factor-Β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells

S. Ehata, E. Johansson, R. Katayama, S. Koike, A. Watanabe, Y. Hoshino, Y. Katsuno, A. Komuro, D. Koinuma, Mitsunobu Kano, M. Yashiro, K. Hirakawa, H. Aburatani, N. Fujita, K. Miyazono

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Stem cells in normal tissues and cancer-initiating cells (CICs) are known to be enriched in side population (SP) cells. However, the factors responsible for the regulation of expression of ABCG2, involved in efflux of dyes, in SP cells have not been fully investigated. Here, we characterized the SP cells within diffuse-type gastric carcinoma, and examined the effects of transforming growth factor-Β (TGF-Β) on SP cells. Diffuse-type gastric carcinoma cells established from four independent patients universally contained SP cells between 1 and 4% of total cells, which displayed greater tumorigenicity than non-SP cells did. TGF-Β repressed the transcription of ABCG2 through direct binding of Smad2/3 to its promoter/enhancer, and the number of SP cells and the tumor-forming ability of cancer cells were decreased by TGF-Β, although ABCG2 is not directly involved in the tumor-forming ability of SP cells. Cancer cells from metastatic site expressed much higher levels of ABCG2 and included a greater percentage of SP cells than parental cancer cells did. SP cells are thus responsible for the progression of diffuse-type gastric carcinoma, and TGF-Β negatively contributes to maintain the CICs within the cancer.

Original languageEnglish
Pages (from-to)1693-1705
Number of pages13
JournalOncogene
Volume30
Issue number14
DOIs
Publication statusPublished - Apr 7 2011
Externally publishedYes

Fingerprint

Side-Population Cells
Transforming Growth Factors
Stomach
Carcinoma
Population
Neoplasms
Coloring Agents
Stem Cells

Keywords

  • ABCG2
  • cancer-initiating cell
  • diffuse type gastric carcinoma
  • SP cell
  • TGF-β

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Ehata, S., Johansson, E., Katayama, R., Koike, S., Watanabe, A., Hoshino, Y., ... Miyazono, K. (2011). Transforming growth factor-Β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells. Oncogene, 30(14), 1693-1705. https://doi.org/10.1038/onc.2010.546

Transforming growth factor-Β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells. / Ehata, S.; Johansson, E.; Katayama, R.; Koike, S.; Watanabe, A.; Hoshino, Y.; Katsuno, Y.; Komuro, A.; Koinuma, D.; Kano, Mitsunobu; Yashiro, M.; Hirakawa, K.; Aburatani, H.; Fujita, N.; Miyazono, K.

In: Oncogene, Vol. 30, No. 14, 07.04.2011, p. 1693-1705.

Research output: Contribution to journalArticle

Ehata, S, Johansson, E, Katayama, R, Koike, S, Watanabe, A, Hoshino, Y, Katsuno, Y, Komuro, A, Koinuma, D, Kano, M, Yashiro, M, Hirakawa, K, Aburatani, H, Fujita, N & Miyazono, K 2011, 'Transforming growth factor-Β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells', Oncogene, vol. 30, no. 14, pp. 1693-1705. https://doi.org/10.1038/onc.2010.546
Ehata, S. ; Johansson, E. ; Katayama, R. ; Koike, S. ; Watanabe, A. ; Hoshino, Y. ; Katsuno, Y. ; Komuro, A. ; Koinuma, D. ; Kano, Mitsunobu ; Yashiro, M. ; Hirakawa, K. ; Aburatani, H. ; Fujita, N. ; Miyazono, K. / Transforming growth factor-Β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells. In: Oncogene. 2011 ; Vol. 30, No. 14. pp. 1693-1705.
@article{51467b5128a94a98a9e23aa272f8e9f3,
title = "Transforming growth factor-Β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells",
abstract = "Stem cells in normal tissues and cancer-initiating cells (CICs) are known to be enriched in side population (SP) cells. However, the factors responsible for the regulation of expression of ABCG2, involved in efflux of dyes, in SP cells have not been fully investigated. Here, we characterized the SP cells within diffuse-type gastric carcinoma, and examined the effects of transforming growth factor-Β (TGF-Β) on SP cells. Diffuse-type gastric carcinoma cells established from four independent patients universally contained SP cells between 1 and 4{\%} of total cells, which displayed greater tumorigenicity than non-SP cells did. TGF-Β repressed the transcription of ABCG2 through direct binding of Smad2/3 to its promoter/enhancer, and the number of SP cells and the tumor-forming ability of cancer cells were decreased by TGF-Β, although ABCG2 is not directly involved in the tumor-forming ability of SP cells. Cancer cells from metastatic site expressed much higher levels of ABCG2 and included a greater percentage of SP cells than parental cancer cells did. SP cells are thus responsible for the progression of diffuse-type gastric carcinoma, and TGF-Β negatively contributes to maintain the CICs within the cancer.",
keywords = "ABCG2, cancer-initiating cell, diffuse type gastric carcinoma, SP cell, TGF-β",
author = "S. Ehata and E. Johansson and R. Katayama and S. Koike and A. Watanabe and Y. Hoshino and Y. Katsuno and A. Komuro and D. Koinuma and Mitsunobu Kano and M. Yashiro and K. Hirakawa and H. Aburatani and N. Fujita and K. Miyazono",
year = "2011",
month = "4",
day = "7",
doi = "10.1038/onc.2010.546",
language = "English",
volume = "30",
pages = "1693--1705",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "14",

}

TY - JOUR

T1 - Transforming growth factor-Β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells

AU - Ehata, S.

AU - Johansson, E.

AU - Katayama, R.

AU - Koike, S.

AU - Watanabe, A.

AU - Hoshino, Y.

AU - Katsuno, Y.

AU - Komuro, A.

AU - Koinuma, D.

AU - Kano, Mitsunobu

AU - Yashiro, M.

AU - Hirakawa, K.

AU - Aburatani, H.

AU - Fujita, N.

AU - Miyazono, K.

PY - 2011/4/7

Y1 - 2011/4/7

N2 - Stem cells in normal tissues and cancer-initiating cells (CICs) are known to be enriched in side population (SP) cells. However, the factors responsible for the regulation of expression of ABCG2, involved in efflux of dyes, in SP cells have not been fully investigated. Here, we characterized the SP cells within diffuse-type gastric carcinoma, and examined the effects of transforming growth factor-Β (TGF-Β) on SP cells. Diffuse-type gastric carcinoma cells established from four independent patients universally contained SP cells between 1 and 4% of total cells, which displayed greater tumorigenicity than non-SP cells did. TGF-Β repressed the transcription of ABCG2 through direct binding of Smad2/3 to its promoter/enhancer, and the number of SP cells and the tumor-forming ability of cancer cells were decreased by TGF-Β, although ABCG2 is not directly involved in the tumor-forming ability of SP cells. Cancer cells from metastatic site expressed much higher levels of ABCG2 and included a greater percentage of SP cells than parental cancer cells did. SP cells are thus responsible for the progression of diffuse-type gastric carcinoma, and TGF-Β negatively contributes to maintain the CICs within the cancer.

AB - Stem cells in normal tissues and cancer-initiating cells (CICs) are known to be enriched in side population (SP) cells. However, the factors responsible for the regulation of expression of ABCG2, involved in efflux of dyes, in SP cells have not been fully investigated. Here, we characterized the SP cells within diffuse-type gastric carcinoma, and examined the effects of transforming growth factor-Β (TGF-Β) on SP cells. Diffuse-type gastric carcinoma cells established from four independent patients universally contained SP cells between 1 and 4% of total cells, which displayed greater tumorigenicity than non-SP cells did. TGF-Β repressed the transcription of ABCG2 through direct binding of Smad2/3 to its promoter/enhancer, and the number of SP cells and the tumor-forming ability of cancer cells were decreased by TGF-Β, although ABCG2 is not directly involved in the tumor-forming ability of SP cells. Cancer cells from metastatic site expressed much higher levels of ABCG2 and included a greater percentage of SP cells than parental cancer cells did. SP cells are thus responsible for the progression of diffuse-type gastric carcinoma, and TGF-Β negatively contributes to maintain the CICs within the cancer.

KW - ABCG2

KW - cancer-initiating cell

KW - diffuse type gastric carcinoma

KW - SP cell

KW - TGF-β

UR - http://www.scopus.com/inward/record.url?scp=79953788906&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953788906&partnerID=8YFLogxK

U2 - 10.1038/onc.2010.546

DO - 10.1038/onc.2010.546

M3 - Article

C2 - 21132002

AN - SCOPUS:79953788906

VL - 30

SP - 1693

EP - 1705

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 14

ER -