Neuroblastoma (NB) is the most common extracranial solid tumour in infants. Unfortunately, most children present with advanced disease and have a poor prognosis. In the present study, we evaluated the role of the peroxisome proliferator-activated receptor g (PPARg) agonist rosiglitazone (RGZ) in two NB cell lines (SK-N-AS and SH-SY5Y), which express PPARg. Rosiglitazone decreased cell proliferation and viability to a greater extent in SK-N-AS than in SH-SY5Y. Furthermore, 20 mM RGZ significantly inhibited cell adhesion, invasiveness and apoptosis in SK-N-AS, but not in SH-SY5Y. Because of the different response of SK-N-AS and SH-SY5Y cells to RGZ, the function of PPARg as a transcriptional activator was assessed. Noticeably, transient transcription experiments with a PPARg responsive element showed that RGZ induced a three-fold increase of the reporter activity in SK-N-AS, whereas no effect was observed in SH-SY5Y. The different PPARg activity may be likely due to the markedly lower amount of phopshorylated (i.e. inactive) protein observed in SK-N-AS. To our knowledge, this is the first demonstration that the differential response of NB cells to RGZ may be related to differences in PPARg transactivation. This finding indicates that PPARg activity may be useful to select those patients, for whom PPARg agonists may have a beneficial therapeutic effect

Antineoplastic effects of rosiglitazone and PPARgamma transactivation in neuroblastoma cells / CELLAI I; BENVENUTI S; LUCIANI P; GALLI A; CENI E; SIMI L; BAGLIONI S; MURATORI M; OTTANELLI B; M. SERIO; THIELE CJ; PERI A. - In: BRITISH JOURNAL OF CANCER. - ISSN 0007-0920. - STAMPA. - 95:(2006), pp. 879-888.

Antineoplastic effects of rosiglitazone and PPARgamma transactivation in neuroblastoma cells

CELLAI, ILARIA;BENVENUTI, SUSANNA;LUCIANI, PAOLA;GALLI, ANDREA;CENI, ELISABETTA;SIMI, LISA;BAGLIONI, SILVANA;MURATORI, MONICA;SERIO, MARIO;PERI, ALESSANDRO
2006

Abstract

Neuroblastoma (NB) is the most common extracranial solid tumour in infants. Unfortunately, most children present with advanced disease and have a poor prognosis. In the present study, we evaluated the role of the peroxisome proliferator-activated receptor g (PPARg) agonist rosiglitazone (RGZ) in two NB cell lines (SK-N-AS and SH-SY5Y), which express PPARg. Rosiglitazone decreased cell proliferation and viability to a greater extent in SK-N-AS than in SH-SY5Y. Furthermore, 20 mM RGZ significantly inhibited cell adhesion, invasiveness and apoptosis in SK-N-AS, but not in SH-SY5Y. Because of the different response of SK-N-AS and SH-SY5Y cells to RGZ, the function of PPARg as a transcriptional activator was assessed. Noticeably, transient transcription experiments with a PPARg responsive element showed that RGZ induced a three-fold increase of the reporter activity in SK-N-AS, whereas no effect was observed in SH-SY5Y. The different PPARg activity may be likely due to the markedly lower amount of phopshorylated (i.e. inactive) protein observed in SK-N-AS. To our knowledge, this is the first demonstration that the differential response of NB cells to RGZ may be related to differences in PPARg transactivation. This finding indicates that PPARg activity may be useful to select those patients, for whom PPARg agonists may have a beneficial therapeutic effect
2006
95
879
888
CELLAI I; BENVENUTI S; LUCIANI P; GALLI A; CENI E; SIMI L; BAGLIONI S; MURATORI M; OTTANELLI B; M. SERIO; THIELE CJ; PERI A
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/223537
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