Chagnovich D, Cohn S L
Program in Tumor Cell Biology, Robert H. Lurie Cancer Center, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Eur J Cancer. 1997 Oct;33(12):2064-7. doi: 10.1016/s0959-8049(97)00208-6.
Subclones of neuroblastic (N) and substrate adherent (S) cells have been established from neuroblastoma tumours cultured in vitro which differ in growth characteristics and MYCN expression. N cells derived from the NBL-W cell line (W-N) express 5-fold higher levels of MYCN mRNA and 10-fold higher levels of MYCN protein than S cells (W-S), despite having the same MYCN copy number. In an effort to identify the molecular mechanisms responsible for the disparity in steady-state MYCN levels, the rate of MYCN mRNA degradation was measured in the two subclones. The half-life of MYCN mRNA in the W-N cells was approximately 45 min compared to approximately 6 min in the W-S cells. Similarly, the half-life of another labile mRNA, c-fos, differed in W-N and W-S cells (30 min versus 15 min, respectively). The turnover of labile mRNAs is thought to be mediated by the interactions of trans-acting factors with AU-rich elements within the 3' untranslated region. RNA UV cross-linking assays using W-N cell lysate demonstrated abundant quantities of a protein, 40 kDa in size (p40), that bound specifically to AU-rich elements within the MYCN and c-fos 3' untranslated region. However, p40 was barely detectable in W-S cells. Our studies suggest that p40 may play a role in determining neuroblastoma phenotype by regulating MYCN and c-fos mRNA turnover.
