Analysis of tumor-suppressor gene in pediatric malignant brain tumors

突变型P53基因产物在34%的髓母细胞瘤、22%的室管膜瘤和47%的其他脑胶质瘤中均有表达，而在正常脑组织包括小脑中未见表达。原位杂交法分析突变型P53基因的mRNA定位与突变型P53基因产物的定位结果基本一致。MIB1指数高的组织中突变型P53基因产物高表达。在原始神经外胚层肿瘤中，神经生长因子受体(NGF-R)在髓母细胞瘤等未成熟神经源性肿瘤中表达。我们从人髓母细胞瘤细胞系(MED-3)中筛选出原肌球蛋白受体激酶(Trk)阳性细胞和低亲和力NGF-R阳性细胞亚克隆，并检测其对NGF的反应性。Trk阳性亚克隆显示NGF诱导分化和抑制细胞生长。此外，Trk阳性的髓母细胞瘤的预后好于Trk阴性的髓母细胞瘤。突变型P53基因产物的表达与预后、复发时间、耐药责任无关。以上结果提示，trk原癌基因是髓母细胞瘤分化的靶基因。

The expression of mutant p53 gene product was found in 34% mudulloblastoma, 22% ependymoma, and 47% other gliomas in various pediatric brain tumors, although it was not found in normal brain tissues including cerebellum. And also, the localization of mRNA of mutan p53 gene analyzed by in situ hybridization was the almost same localization of mutant p53 gene product. And also, the tissues with high MIB1 index were shown the high expression of mutant p53 gene product. It was correlated between the growth potential and the expression of mutant p53 gene product.In primitive neuroectodermal tumors, nerve growth factor receptor (NGF-R) was expressed in immature neurogenic tumors, such as medulloblastoma.. We selected the subclones of tropomyosin receptor kinase (trk) -positive cells and low-affinity NGF-R-positive cells from human medullobrastoma cell line (MED-3) and examine the responsibility against NGF.Trk-positive subclone showed the induction of differentiation and the inhibition of cell growth inducd by NGF.It was suggested the role of trk gene protooncogene in differentiation of medulloblastoma. Furthermore, the prognosis in trk-positive medulloblastoma was better than that in trk-negative medulloblastoma. On the otherhand, there was no correlation between the prognosis, the period of recurrence and the responsibility against treatment and the expression of mutant p53 gene product. From the above results, it was suggested that trk protooncogene is the target gene in differentiation of medulloblastoma.