PPARγ ligands suppress the feedback loop between E2F2 and cyclin-E1

Yoko Komatsu, Ichiaki Ito, Mitsutoshi Wayama, Akiko Fujimura, Kensuke Akaogi, Hikaru Machida, Yuka Nakajima, Takao Kuroda, Kazuji Ohmori, Akiko Murayama, Keiji Kimura, Junn Yanagisawa

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

PPARγ is a nuclear hormone receptor that plays a key role in the induction of peroxisome proliferation. A number of studies showed that PPARγ ligands suppress cell cycle progression; however, the mechanism remains to be determined. Here, we showed that PPARγ ligand troglitazone inhibited G1/S transition in colon cancer cells, LS174T. Troglitazone did not affect on either expression of CDK inhibitor (p18) or Wnt signaling pathway, indicating that these pathways were not involved in the troglitazone-dependent cell cycle arrest. GeneChip and RT-PCR analyses revealed that troglitazone decreased mRNA levels of cell cycle regulatory factors E2F2 and cyclin-E1 whose expression is activated by E2F2. Down-regulation of E2F2 by troglitazone results in decrease of cyclin-E1 transcription, which could inhibit phosphorylation of Rb protein, and consequently evoke the suppression of E2F2 transcriptional activity. Thus, we propose that troglitazone suppresses the feedback loop containing E2F2, cyclin-E1, and Rb protein.

Original languageEnglish (US)
Pages (from-to)145-148
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume370
Issue number1
DOIs
StatePublished - May 23 2008
Externally publishedYes

Fingerprint

troglitazone
Peroxisome Proliferator-Activated Receptors
Cyclins
Ligands
Feedback
Cells
Retinoblastoma Protein
Cell Cycle
Phosphorylation
Wnt Signaling Pathway
Peroxisomes
Transcription
Cytoplasmic and Nuclear Receptors
Cell Cycle Checkpoints
Colonic Neoplasms
Down-Regulation

Keywords

  • Cyclin-E1
  • E2F2
  • PPARγ
  • Troglitazone
  • Wnt signal

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

PPARγ ligands suppress the feedback loop between E2F2 and cyclin-E1. / Komatsu, Yoko; Ito, Ichiaki; Wayama, Mitsutoshi; Fujimura, Akiko; Akaogi, Kensuke; Machida, Hikaru; Nakajima, Yuka; Kuroda, Takao; Ohmori, Kazuji; Murayama, Akiko; Kimura, Keiji; Yanagisawa, Junn.

In: Biochemical and Biophysical Research Communications, Vol. 370, No. 1, 23.05.2008, p. 145-148.

Research output: Contribution to journalArticle

Komatsu, Y, Ito, I, Wayama, M, Fujimura, A, Akaogi, K, Machida, H, Nakajima, Y, Kuroda, T, Ohmori, K, Murayama, A, Kimura, K & Yanagisawa, J 2008, 'PPARγ ligands suppress the feedback loop between E2F2 and cyclin-E1', Biochemical and Biophysical Research Communications, vol. 370, no. 1, pp. 145-148. https://doi.org/10.1016/j.bbrc.2008.03.046
Komatsu, Yoko ; Ito, Ichiaki ; Wayama, Mitsutoshi ; Fujimura, Akiko ; Akaogi, Kensuke ; Machida, Hikaru ; Nakajima, Yuka ; Kuroda, Takao ; Ohmori, Kazuji ; Murayama, Akiko ; Kimura, Keiji ; Yanagisawa, Junn. / PPARγ ligands suppress the feedback loop between E2F2 and cyclin-E1. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 370, No. 1. pp. 145-148.
@article{5d41282a536e49c2838275ef2857da6a,
title = "PPARγ ligands suppress the feedback loop between E2F2 and cyclin-E1",
abstract = "PPARγ is a nuclear hormone receptor that plays a key role in the induction of peroxisome proliferation. A number of studies showed that PPARγ ligands suppress cell cycle progression; however, the mechanism remains to be determined. Here, we showed that PPARγ ligand troglitazone inhibited G1/S transition in colon cancer cells, LS174T. Troglitazone did not affect on either expression of CDK inhibitor (p18) or Wnt signaling pathway, indicating that these pathways were not involved in the troglitazone-dependent cell cycle arrest. GeneChip and RT-PCR analyses revealed that troglitazone decreased mRNA levels of cell cycle regulatory factors E2F2 and cyclin-E1 whose expression is activated by E2F2. Down-regulation of E2F2 by troglitazone results in decrease of cyclin-E1 transcription, which could inhibit phosphorylation of Rb protein, and consequently evoke the suppression of E2F2 transcriptional activity. Thus, we propose that troglitazone suppresses the feedback loop containing E2F2, cyclin-E1, and Rb protein.",
keywords = "Cyclin-E1, E2F2, PPARγ, Troglitazone, Wnt signal",
author = "Yoko Komatsu and Ichiaki Ito and Mitsutoshi Wayama and Akiko Fujimura and Kensuke Akaogi and Hikaru Machida and Yuka Nakajima and Takao Kuroda and Kazuji Ohmori and Akiko Murayama and Keiji Kimura and Junn Yanagisawa",
year = "2008",
month = "5",
day = "23",
doi = "10.1016/j.bbrc.2008.03.046",
language = "English (US)",
volume = "370",
pages = "145--148",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - PPARγ ligands suppress the feedback loop between E2F2 and cyclin-E1

AU - Komatsu, Yoko

AU - Ito, Ichiaki

AU - Wayama, Mitsutoshi

AU - Fujimura, Akiko

AU - Akaogi, Kensuke

AU - Machida, Hikaru

AU - Nakajima, Yuka

AU - Kuroda, Takao

AU - Ohmori, Kazuji

AU - Murayama, Akiko

AU - Kimura, Keiji

AU - Yanagisawa, Junn

PY - 2008/5/23

Y1 - 2008/5/23

N2 - PPARγ is a nuclear hormone receptor that plays a key role in the induction of peroxisome proliferation. A number of studies showed that PPARγ ligands suppress cell cycle progression; however, the mechanism remains to be determined. Here, we showed that PPARγ ligand troglitazone inhibited G1/S transition in colon cancer cells, LS174T. Troglitazone did not affect on either expression of CDK inhibitor (p18) or Wnt signaling pathway, indicating that these pathways were not involved in the troglitazone-dependent cell cycle arrest. GeneChip and RT-PCR analyses revealed that troglitazone decreased mRNA levels of cell cycle regulatory factors E2F2 and cyclin-E1 whose expression is activated by E2F2. Down-regulation of E2F2 by troglitazone results in decrease of cyclin-E1 transcription, which could inhibit phosphorylation of Rb protein, and consequently evoke the suppression of E2F2 transcriptional activity. Thus, we propose that troglitazone suppresses the feedback loop containing E2F2, cyclin-E1, and Rb protein.

AB - PPARγ is a nuclear hormone receptor that plays a key role in the induction of peroxisome proliferation. A number of studies showed that PPARγ ligands suppress cell cycle progression; however, the mechanism remains to be determined. Here, we showed that PPARγ ligand troglitazone inhibited G1/S transition in colon cancer cells, LS174T. Troglitazone did not affect on either expression of CDK inhibitor (p18) or Wnt signaling pathway, indicating that these pathways were not involved in the troglitazone-dependent cell cycle arrest. GeneChip and RT-PCR analyses revealed that troglitazone decreased mRNA levels of cell cycle regulatory factors E2F2 and cyclin-E1 whose expression is activated by E2F2. Down-regulation of E2F2 by troglitazone results in decrease of cyclin-E1 transcription, which could inhibit phosphorylation of Rb protein, and consequently evoke the suppression of E2F2 transcriptional activity. Thus, we propose that troglitazone suppresses the feedback loop containing E2F2, cyclin-E1, and Rb protein.

KW - Cyclin-E1

KW - E2F2

KW - PPARγ

KW - Troglitazone

KW - Wnt signal

UR - http://www.scopus.com/inward/record.url?scp=41849137521&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41849137521&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2008.03.046

DO - 10.1016/j.bbrc.2008.03.046

M3 - Article

VL - 370

SP - 145

EP - 148

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 1

ER -