Study on Oncogenes and Growth-Related Antigens of Human Brain Tumors

已有研究表明，第17号染色体短臂(17p)和第10号染色体长臂(10q)的等位基因缺失与人类恶性胶质瘤的发生密切相关。最近的研究表明，编码在染色体17p13.1上的细胞P53基因可能作为肿瘤生长的抑制因子，在人类神经胶质瘤的发病机制中发挥重要作用。我们重点研究了P53基因异常与人脑胶质瘤发生发展的关系，并对P53蛋白在胶质瘤中的结构和表达以及P53基因突变进行了研究。我们的研究表明，几种胶质瘤细胞系的P53蛋白不仅在表达上存在异常，而且在分子结构上也存在异常，P53的异常可能是与胶质瘤发生有关的一个重要事件。免疫电子显微镜显示Ki-67阳性反应位于核仁的颗粒状和致密成分上，提示Ki-67可能参与了胸前颗粒的加工和组装。另一方面，PCR-SSCP(聚合酶链式反应-单链构象多态)分析发现，在7个人神经胶质细胞系中，有3个发生了核苷酸替换，这些细胞株位于p53基因的第7或8外显子，通常在物种上保守。我们认为这些P53基因编码序列的遗传改变是相当负责任的突变，因为它们的产物显示出延长的半衰期，并在人神经胶质瘤细胞的细胞核中持续表达。由此可见，P53基因的突变在胶质细胞瘤的发生发展中起着重要的作用。

Previous studies have demonstrated that the allelic deletions of the short arm of chromosome seventeenth (17p) and the long arm of the tenth (10q) are closely associated with the tumorigenesis of human malignant gliomas. Recent studies have shown that the cellular p53, which is encoded on chromosome17p13.1, may function as a suppressor of neoplastic growth and play an important role in the pathogenesis of human glial tumors. We have focused on the genetic abnormalities of p53 in relation to the development of human glial tumors, and investigated the structure and expression of p53 protein in glial tumors as well as the mutations of p53 gene. Our study demonstrated that several glioma cell lines had an aberrant form of p53 protein not only in its expression but also its molecular structure, and that p53 abnormalities might be an essential event associated with development of glial tumors. Immunoelectron microscopic study revealed that positive reaction for Ki-67 was on the granular and dense components of nucleolus, indicating that Ki-67 might participate in the processing and assembly of preribosmal particles. On the other hand, PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) analysis disclosed nucleotide substitution in 3 out of 7 human glial cell lines examined in exon 7 or 8 of the p53 gene, which were generally conserved over species. We assume these genetic alterations in coding sequence of the p53 gene are quite responsible mutations, because their products show prolonged half-life and are constantly expressed in the nuclei of human glial tumor cells. In view of these points, the genetic alterations of p53 gene appear to play a significant role in the development of glial cell neoplasia.