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 language | English (US) |
|---|---|
| Pages (from-to) | 145-148 |
| Number of pages | 4 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 370 |
| Issue number | 1 |
| DOIs | |
| State | Published - May 23 2008 |
| Externally published | Yes |
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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 journal › Article
}
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 -