Abstract | BACKGROUND: METHODS: RESULTS: The biologic effects of these compounds depend largely on ligand concentration and the degree of PPARgamma activation. For example, low concentrations of 15dPGJ2 (<2.5 microM) and TGZ (<5 microM) increased cellular proliferation, but concentrations of 15dPGJ2 > or = 10 microM and of TGZ at 100 microM blocked cell growth. TGZ (100 microM) slowed cell cycle progression, and 15dPGJ2 (10 microM) caused an S-phase arrest in the cell cycle and induced morphological characteristics consistent with apoptosis. Expression of CD36, a marker of differentiation in these cells, was induced by 2.5 microM 15dPGJ2 or 5 to 100 microM TGZ. However, higher concentrations of 15dPGJ2 did not alter CD36 expression. Transcriptional activation studies demonstrated that 15dPGJ2 is a more potent PPARgamma ligand than TGZ. Regardless of the ligand used, though, low transcriptional activation correlated with an increased cellular proliferation, whereas higher levels of activation correlated with cell cycle arrest and apoptosis. CONCLUSIONS:
PPARgamma activation induces several important and seemingly opposite changes in neoplastic cells, depending on the magnitude of PPARgamma activation. These data may explain, at least in part, some of the discordant results previously reported.
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Authors | C E Clay, A M Namen, G Atsumi, A J Trimboli, A N Fonteh, K P High, F H Chilton |
Journal | Journal of investigative medicine : the official publication of the American Federation for Clinical Research
(J Investig Med)
Vol. 49
Issue 5
Pg. 413-20
(Sep 2001)
ISSN: 1081-5589 [Print] England |
PMID | 11523697
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- 15-deoxy-delta(12,14)-prostaglandin J2
- Chromans
- Receptors, Cytoplasmic and Nuclear
- Thiazoles
- Thiazolidinediones
- Transcription Factors
- Troglitazone
- Prostaglandin D2
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Topics |
- Apoptosis
(drug effects)
- Breast Neoplasms
(pathology)
- Cell Cycle
(drug effects)
- Cell Differentiation
(drug effects)
- Cell Division
(drug effects)
- Chromans
(pharmacology)
- Female
- Humans
- Prostaglandin D2
(analogs & derivatives, pharmacology)
- Receptors, Cytoplasmic and Nuclear
(physiology)
- Thiazoles
(pharmacology)
- Thiazolidinediones
- Transcription Factors
(physiology)
- Transcriptional Activation
(drug effects)
- Troglitazone
- Tumor Cells, Cultured
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