SL12 T-LYMPHOMA: A NEW MODEL FOR GENE CONTROL IN TUMORS

这项研究计划利用了一系列克隆细胞系， 肿瘤发展的动力学，原发器官疾病的部位， 几种表面抗原的表达和糖皮质激素反应性。 所有细胞系均来源于单个AKR自发性T淋巴瘤， 使用三种方法获得：（1）原始细胞系是 克隆;（2）采用体外筛选方法， 分离具有不同表型的亚克隆;和（3） 在体内接种后从动物的各种组织中获得。 一 T细胞成熟阶段特征性表型改变的数量 已经在这些细胞克隆中鉴定出， α和β T细胞抗原受体mRNA的量。 这样做的目的 工作是检查表型的程度和分子性质， 并将这些差异与致瘤性和肿瘤 同基因动物的进展。 我们研究计划的目标是 分离T淋巴瘤与正常人之间差异表达的基因， 致瘤性和体内生长显著不同的细胞克隆 特性. 为此，已经构建了λ gt 11文库。 的 表面抗原表达的表型差异已经 将提供检测方法，用于监测 提出了分离差异表达基因的方法。 的 将通过以下方法检查差异表达基因的调节 测量转录率和DNA甲基化模式。 并发 将进行实验以测试低致瘤性细胞是否 克隆可以在连续传代后产生更多的致瘤性表型， vivo. 差异基因表达将比较之间的， 体内来源的致瘤细胞系和原始的高度致瘤性 分身 结合分子和细胞研究的研究将产生 关于肿瘤细胞异质性和肿瘤的新的和有价值的信息 进展 （S）

This research plan exploits a series of cloned cell lines which differs in the kinetics of tumor development, the site of primary organ disease, the expression of several surface antigens, and glucocorticoid responsiveness. All the cell lines originated from a single AKR spontaneous T lymphoma and were derived using three approaches: (1)\the original cell line was cloned; (2)\in vitro selection methods were applied which were designed to isolate subclones with differing phenotypes; and (3)\cell clones were obtained from various tissues of animals following in vivo inoculation. A number of phenotypic alterations characteristic of T-cell maturation stages have been identified among these cell clones including differences in the amount of alpha and beta T-cell antigen receptor mRNA. The purpose of this work is to examine the extent and molecular nature of the phenotypic heterogeneity and to relate those differences to tumorigenicity and tumor progression in syngeneic animals. The goal of our research plan is to isolate the genes which are differentially expressed between T-lymphoma cell clones which differ significantly in tumorigenicity and in vivo growth properties. To this end, lamda gt 11 libraries have been constructed. The phenotypic differences in the expression of surface antigens already identified will provide assays with which to monitor the effectiveness of the proposed methods to isolate differentially expressed genes. The regulation of the differentially expressed genes will be examined by measuring the transcription rates and DNA methylation patterns. Concurrent experiments will be undertaken to test whether the poorly tumorigenic cell clone can give rise to a more tumorigenic phenotype upon serial passage in vivo. Differential gene expression will be compared between the in vivo-derived tumorigenic cell line and an original highly tumorigenic clone. The research combining molecular and cellular studies will yield new and valuable information on tumor cell heterogeneity and tumor progression. (S)