Caspase‐8 Gene Expression in Neuroblastoma

• DOI: 10.1196/annals.1322.017
• Publication Date: 2005-01-13T20:08:46Z
• Authors: IDA CASCIANO; BARBARA BANELLI; MICHELA CROCE; ALESSANDRO DE AMB...; ANGELA Di VINCI; ILARIA GELVI; GABRIELLA PAGNAN; CHIARA BRIGNOLE; GIORGIO ALLEMANNI; SILVANO FERRINI; MIRCO PONZONI; MASSIMO ROMANI
• Keywords: Survivin; Demethylating agent; CpG site

A bstract : Neuroblastoma (NB) is a solid tumor of infancy that presents high rate spontaneous regression, phenomenon likely reflects the activation an apoptotic/differentiation program. Indeed, level expression molecules involved in regulation apoptosis, such as p73 or survivin, prognostic factor NB patients. The caspase‐8 gene (CASP8) encodes key enzyme at top apoptotic cascade. Although methylation putative regulatory region CASP8 reportedly inhibits its transcription some MYCN ‐amplified NB, our results indicate transcriptional inactivation occurs subset primary independently amplification CpG methylation. In addition, agent fenretinide (4HPR) and interferon‐γ (IFN‐γ) induce without modifying status this gene. Nevertheless, intragenic promoter regions higher tumors compared to nonamplified samples. This might reflect existence distinct DNA errors ‐single copy tumors. To gain information on mechanisms regulate crucial gene, we searched for potential cloned element 5′ terminus functionally acts only cell lines express caspase‐8. retinoic acid analogue 4HPR, IFN‐γ, demethylating 5‐aza‐cytidine activate cells lack endogenous caspase‐8, indicating may both constitutive inducible expression. These also demethylation cellular genome upregulate through action trans ‐acting factors. Our provide new insights CASP8, with essential role variety physiologic pathologic conditions.