Thiele C J, Deutsch L A, Israel M A
Molecular Genetics Section, National Cancer Institute, Bethesda, Maryland 20892.
Oncogene. 1988 Sep;3(3):281-8.
Human neuroblastoma (NB) is a highly malignant tumor arising in cells that originate in the embryonal neural crest. Several lines of investigation suggest that both NB and other tumors of developing tissues are blocked in their ability to differentiate and achieve growth arrest. Since in vivo differentiation of NB has been frequently observed and may be of clinical importance (Fox et al., 1959; Evans et al., 1976), we have utilized the in vitro induction of NB differentiation by retinoic acid (RA) to study the molecular events associated with NB differentiation. We have focused our studies on changes that occur in the expression of various proto-oncogenes during NB tumors cell differentiation because proto-oncogenes are likely to be of central importance in mediating processes critical for cellular growth and maturation. In these studies, we have found that the expression of no fewer than five proto-oncogenes including c-Ha-ras, c-ets-1, and c-fos change during the differentiation of NB cells, while the expression of c-erb-B changes in association with the arrest of growth that occurs during NB differentiation. In some cases the altered expression of a proto-oncogene was transcriptionally regulated, while in others post-transcriptional mechanisms were important.
人类神经母细胞瘤（NB）是一种起源于胚胎神经嵴细胞的高度恶性肿瘤。多项研究表明，NB以及其他发育组织肿瘤在分化和实现生长停滞的能力方面受到阻碍。由于NB在体内的分化现象经常被观察到，并且可能具有临床意义（Fox等人，1959年；Evans等人，1976年），我们利用视黄酸（RA）在体外诱导NB分化，以研究与NB分化相关的分子事件。我们的研究重点是NB肿瘤细胞分化过程中各种原癌基因表达的变化，因为原癌基因可能在介导细胞生长和成熟的关键过程中起着核心作用。在这些研究中，我们发现至少有五个原癌基因的表达在NB细胞分化过程中发生变化，包括c-Ha-ras、c-ets-1和c-fos，而c-erb-B的表达变化与NB分化过程中发生的生长停滞有关。在某些情况下，原癌基因表达的改变是由转录调控的，而在其他情况下，转录后机制则很重要。
