Mendonca M S, Howard K, Fasching C L, Farrington D L, Desmond L A, Stanbridge E J, Redpath J L
Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis 46202, USA.
Radiat Res. 1998 Mar;149(3):246-55.
We have previously reported a linkage between radiation-induced damage to a putative tumor suppressor locus on fibroblast chromosome 11 and the re-expression of tumorigenicity in a hybrid cell line (HeLa x human skin fibroblast) used to study neoplastic transformation. Further investigation into the molecular basis of radiation-induced neoplastic transformation of the hybrid cell, CGL1, indicates that loss of fibroblast chromosome 11 appears to be necessary but not sufficient for neoplastic transformation. Previous analysis had suggested, though not clearly demonstrated, a possible role for loss of alleles on fibroblast chromosome 14 in the neoplastic transformation of the hybrid cells. Therefore, the status of chromosome 14 in the gamma-ray-induced, neoplastically transformed (GIM) hybrid cell lines and in nontumorigenic control (CON) hybrid cell lines isolated from irradiated populations has been investigated. Chromosome painting and molecular studies using restriction fragment length polymorphisms and tetranucleotide repeat polymorphism analysis were performed. As an additional control, the status of chromosome 12 was also examined. We report that five of the eight GIM cell lines have lost one complete copy of a fibroblast chromosome 14 while only one of the five CON cell lines has lost a complete copy of a fibroblast chromosome 14. No evidence of large-scale loss of chromosome 12 was detected in the GIM or CON cells. The data further suggest that both copies of fibroblast chromosome 14 contain an active tumor suppressor locus and that radiation-induced loss of either fibroblast chromosome 14 is associated with neoplastic transformation in this system. We now conclude that loss of alleles on both fibroblast chromosome 11 and 14 may be required for the radiation-induced neoplastic transformation of these human hybrid cells.
我们之前曾报道过，在用于研究肿瘤转化的杂交细胞系（HeLa×人皮肤成纤维细胞）中，辐射诱导对成纤维细胞11号染色体上一个假定的肿瘤抑制基因座的损伤与肿瘤igenicity的重新表达之间存在联系。对杂交细胞CGL1辐射诱导的肿瘤转化的分子基础的进一步研究表明，成纤维细胞11号染色体的缺失似乎是肿瘤转化所必需的，但并不充分。先前的分析虽未明确证明，但提示成纤维细胞14号染色体上等位基因的缺失在杂交细胞的肿瘤转化中可能起作用。因此，研究了γ射线诱导的肿瘤转化（GIM）杂交细胞系和从受辐照群体中分离出的非致瘤对照（CON）杂交细胞系中14号染色体的状态。进行了染色体涂染以及使用限制性片段长度多态性和四核苷酸重复多态性分析的分子研究。作为额外对照，还检查了12号染色体的状态。我们报告说，八个GIM细胞系中有五个丢失了一条完整的成纤维细胞14号染色体拷贝，而五个CON细胞系中只有一个丢失了一条完整的成纤维细胞14号染色体拷贝。在GIM或CON细胞中未检测到12号染色体大规模缺失的证据。数据进一步表明，成纤维细胞14号染色体的两个拷贝都含有一个活跃的肿瘤抑制基因座，并且在该系统中，辐射诱导的任何一条成纤维细胞14号染色体的缺失都与肿瘤转化相关。我们现在得出结论，这些人杂交细胞的辐射诱导肿瘤转化可能需要成纤维细胞11号和14号染色体上等位基因的缺失。
