title: PPARgamma ligands suppress the feedback loop between E2F2 and cyclin-E1.
abstract: PPARgamma is a nuclear hormone receptor that plays a key role in the induction of peroxisome proliferation. A number of studies showed that PPARgamma ligands suppress cell cycle progression; however, the mechanism remains to be determined. Here, we showed that PPARgamma 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.
authors: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan.
authors: Yoko
authors: Y
authors: Komatsu
authors: Ichiaki
authors: I
authors: Ito
authors: Mitsutoshi
authors: M
authors: Wayama
authors: Akiko
authors: A
authors: Fujimura
authors: Kensuke
authors: K
authors: Akaogi
authors: Hikaru
authors: H
authors: Machida
authors: Yuka
authors: Y
authors: Nakajima
authors: Takao
authors: T
authors: Kuroda
authors: Kazuji
authors: K
authors: Ohmori
authors: Akiko
authors: A
authors: Murayama
authors: Keiji
authors: K
authors: Kimura
authors: Junn
authors: J
authors: Yanagisawa
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002839:Chromans / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000378:metabolism*; D019927:Cyclin E / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D050703:E2F2 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008024:Ligands; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D000077288:Troglitazone; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C475820:CCNE1 protein, human; D002839:Chromans; D019927:Cyclin E; D050703:E2F2 Transcription Factor; C493761:E2F2 protein, human; D008024:Ligands; D015513:Oncogene Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D045162:Thiazolidinediones; D051153:Wnt Proteins; D000077288:Troglitazone