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的细胞系，这些克隆细胞系在 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的反应性。 所有细胞系均来源于单个AKR自发性T淋巴瘤 用三种方法得到：(1)原始细胞系 (2)应用体外选择方法，设计了 分离具有不同表型的亚克隆；(3)细胞克隆 从动物体内接种后的各种组织中获得。一个 T细胞成熟阶段特有的表型改变的数量 已经在这些细胞克隆中被发现，包括在 α和βT细胞抗原受体mRNA量。这样做的目的是 工作是检查表型的程度和分子性质 异质性以及这些差异与致瘤性和肿瘤的关系 同基因动物的进展。我们研究计划的目标是 分离T淋巴瘤差异表达基因 在致瘤性和体内生长方面有显著差异的细胞克隆 属性。为此，已经构建了Lamda GT 11库。这个 表面抗原表达的表型差异已经存在 将提供监测其有效性的化验方法 提出的分离差异表达基因的方法。这个 差异表达基因的调节将通过 测量转录速率和DNA甲基化模式。并发 将进行实验以测试致瘤能力差的细胞 克隆可以在连续传代时产生更具致瘤性的表型 活着。我们将比较不同基因的差异表达 体内来源的致瘤细胞系和一株原始的高致瘤性细胞系 克隆人。这项结合了分子和细胞研究的研究将产生 肿瘤细胞异质性与肿瘤的新信息 进步。(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)