Embryonal cancer initiation: MYCN-mediated mechanisms of resistance to cell death causing embryonal cell persistence (original) (raw)

Cancer Research, 2007

Abstract

516 The majority of child cancer arises in embryonal cells which have persisted beyond birth, having failed to undergo cell death following normal organogenesis in utero. The mechanism of embryonal cell persistence, and thus, tumour initiation are unknown. Resistance to spontaneous regression by neuroblasts is an important early step in human neuroblastoma tumorigenesis. We have previously shown that perinatal expression of a MYCN transgene in paravertebral murine neuroblasts mediates transient neuroblast proliferation and resistance to apoptotic cell death, as the first step in neuroblastoma tumorigenesis (Hansford et al., PNAS 2004). Here we analysed the mechanism of resistance to apoptotic cell death in primary ganglion cells from MYCN transgenic, compared with normal mice. MYCN-mediated resistance to cell death was seen in ganglion cells following a variety of different death stimuli: nerve growth factor (NGF) withdrawal, hypoxia, nutrient deprivation and doxorubicin. The mRNA e...

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