Retinoic acid-induced growth arrest and differentiation of neuroblastoma cells are counteracted by N-myc and enhanced by max overexpressions.
Retinoic acid-induced growth arrest and differentiation of neuroblastoma cells are counteracted by N-myc and enhanced by max overexpressions.
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视黄酸诱导的神经母细胞瘤细胞生长停滞和分化可被 N-myc 抵消，并通过最大过表达而增强。
作者：
F. Peverali;D. Orioli;L. Tonon;P. Ciana;G. Bunone;M. Negri;G. Della
N-myc的表达受维甲酸（RA）的负调控，RA可诱导神经母细胞瘤（NB）细胞的生长停滞和分化。然而，N-Myc是否促进NB细胞的生长和/或拮抗神经元分化，或者N-Myc的下调是否作为分化开始的结果，尚未完全确定。通过将N-myc基因构建体转染到这些细胞中，我们发现N-myc的组成型过表达刺激了含有RA的培养基中的增殖，尽管这些细胞仍然对RA有反应，但它们不再能够分化。由于N-Myc的功能似乎是通过与Max的异源二聚化介导的，因此我们也研究了Max在NB细胞中的异位过表达。与N-Myc相反，Max通过增强RA的作用而强烈诱导分化。转染max的细胞在RA治疗的几天内迅速停止生长并完全分化。这些发现表明，与Max相比，N-Myc的相对水平似乎对刺激神经母细胞瘤的生长或分化至关重要，并可能有助于解释神经母细胞瘤的显着临床行为。
N-myc expression is negatively regulated by retinoic acid (RA) which induces the growth arrest and differentiation of neuroblastoma (NB) cells. However, it has not been completely defined whether N-Myc promotes growth and/or antagonises neuronal differentiation of NB cells or whether the down regulation of N-myc occurs as a consequence of the onset of differentiation. By transfecting an N-myc gene construct into these cells, we found that the constitutive overexpression of N-myc stimulated proliferation in RA containing medium and, although these cells were still responsive to RA, they were no longer able to differentiate. Since N-Myc functions appear to be mediated by heterodimerization with Max, the ectopic overexpression of max in NB cells was also investigated. In contrast to N-Myc, Max strongly induced the differentiation by enhancing the effects of RA. Max-transfected cells rapidly arrested growth and differentiated fully within a few days of RA treatment. These findings suggest that the relative levels of N-Myc compared to Max appears to be crucial in stimulating neuroblastoma growth or differentiation, and may contribute to explain the remarkable clinical behaviour of neuroblastomas.