PT  - JOURNAL ARTICLE
AU  - Kirmo Wartiovaara
AU  - Fanie Barnabé-Heider
AU  - Freda D. Miller
AU  - David R. Kaplan
TI  - N-myc Promotes Survival and Induces S-Phase Entry of Postmitotic Sympathetic Neurons
AID  - 10.1523/JNEUROSCI.22-03-00815.2002
DP  - 2002 Feb 01
TA  - The Journal of Neuroscience
PG  - 815--824
VI  - 22
IP  - 3
4099  - http://www.jneurosci.org/content/22/3/815.short
4100  - http://www.jneurosci.org/content/22/3/815.full
SO  - J. Neurosci.2002 Feb 01; 22
AB  - In most postmitotic neurons, expression or activation of proteins that stimulate cell cycle progression or DNA replication results in apoptosis. One potential exception to this generalization is neuroblastoma (NB), a tumor derived from the sympathoadrenal lineage. NBs often express high levels of N-myc, a proto-oncogene that can potently activate key components of the cell cycle machinery. Here, we show that in postmitotic sympathetic neurons, N-myc can induce S-phase entry while protecting neurons from death caused by aberrant cell cycle reentry. Specifically, these experiments demonstrate that expression of N-myc at levels similar to those in NBs caused sympathetic neurons to reenter S-phase, as monitored by 5-bromo-2-deoxyuridine incorporation and expression of cell cycle regulatory proteins, and rescued them from apoptosis induced by withdrawal of their obligate survival factor, nerve growth factor. The N-myc-induced cell cycle entry, but not enhanced survival, was inhibited by coexpression of a constitutively hypophosphorylated form of the retinoblastoma tumor suppressor protein, suggesting that these two effects of N-myc are mediated by separate pathways. In contrast, N-myc did not cause S-phase entry in postmitotic cortical neurons. Thus, N-myc both selectively causes sympathetic neurons to reenter the cell cycle and protects them from apoptosis, potentially contributing to their transformation to NBs.