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Titolo:
TERMINAL DIFFERENTIATION OF HUMAN LIPOSARCOMA CELLS INDUCED BY LIGANDS FOR PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA AND THE RETINOID-X RECEPTOR
Autore:
TONTONOZ P; SINGER S; FORMAN BM; SARRAF P; FLETCHER JA; FLETCHER CDM; BRUN RP; MUELLER E; ALTIOK S; OPPENHEIM H; EVANS RM; SPIEGELMAN BM;
Indirizzi:
SALK INST BIOL STUDIES,GENE EXPRESS LAB LA JOLLA CA 92037 HARVARD UNIV,SCH MED,DANA FARBER CANC INST BOSTON MA 02115 HARVARD UNIV,SCH MED,DEPT CELL BIOL BOSTON MA 02115 SALK INST BIOL STUDIES,HOWARD HUGHES MED INST LA JOLLA CA 92037 BRIGHAM & WOMENS HOSP,DEPT SURG BOSTON MA 02115 BRIGHAM & WOMENS HOSP,DEPT PATHOL BOSTON MA 02115
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 1, volume: 94, anno: 1997,
pagine: 237 - 241
SICI:
0027-8424(1997)94:1<237:TDOHLC>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACUTE PROMYELOCYTIC LEUKEMIA; BINDING-PROTEIN-ALPHA; HIGH-AFFINITY LIGAND; SOFT-TISSUE TUMORS; ADIPOCYTE DIFFERENTIATION; MYXOID LIPOSARCOMA; PPAR-GAMMA; EXPRESSION; FAMILY; ACID;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
37
Recensione:
Indirizzi per estratti:
Citazione:
P. Tontonoz et al., "TERMINAL DIFFERENTIATION OF HUMAN LIPOSARCOMA CELLS INDUCED BY LIGANDS FOR PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA AND THE RETINOID-X RECEPTOR", Proceedings of the National Academy of Sciences of the United Statesof America, 94(1), 1997, pp. 237-241

Abstract

Induction of terminal differentiation represents a promising therapeutic approach to certain human malignancies. The peroxisome proliferator-activated receptor gamma (PPAR gamma) and the retinoid X receptor alpha (RXR alpha) form a heterodimeric complex that functions as a central regulator of adipocyte differentiation. Natural and synthetic ligands for both receptors have been identified. We demonstrate here that PPAR gamma is expressed at high levels in each of the major histologic types of human liposarcoma. Moreover, primary human liposarcoma cells can be induced to undergo terminal differentiation by treatment with the PPAR gamma ligand pioglita-zone, suggesting that the differentiation block in these cells can be overcome by maximal activation of the PPAR pathway, We further demonstrate that RXR-specific ligands are also potent adipogenic agents in cells expressing the PPAR gamma/RXR alpha heterodimer, and that simultaneous treatment of liposarcoma cells withboth PPAR gamma- and RXR-specific ligands results in an additive stimulation of differentiation. Liposarcoma cell differentiation is characterized by accumulation of intracellular lipid, induction of adipocyte-specific genes, and withdrawl from the cell cycle. These results suggest that PPAR gamma ligands such as thiazolidinediones and RXR-specific retinoids may be useful therapeutic agents for the treatment of liposarcoma.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 13:31:39