BUDR DEPENDENCE, MALIGNANCY, AND DIFFERENTIATION

这项研究的长期目标是阐明 在黑色素瘤细胞中调节分化的机制。 的 实验将涉及体细胞遗传学技术（细胞 杂交和基因转移）和胸苷类似物5- 溴脱氧尿苷（BrdU）与 重组DNA 这项研究的具体目的是研究 体细胞杂种中的色素沉着，成纤维细胞的转移， 酪氨酸酶基因的杂交，和抑制色素沉着的BrdU。 细胞杂交的实验将集中在染色体上 导致灭绝的调节元件的定位， 灭火器所在地的识别， 反式激活，DNA序列的鉴定（推测 上游）参与调控的酪氨酸酶基因， 分析这些序列影响基因表达的方式。 的 用BrdU进行的实验将集中在DNA序列的鉴定上 在酪氨酸酶基因参与抑制，分析 这些序列的作用方式，以及角色的确定， BrdU在调节因子和调节因子之间的相互作用 酪氨酸酶基因的区域。 这些实验应该会导致 参与的顺式和反式作用调节元件的鉴定 酪氨酸酶基因表达的调控，以鉴定 与这些元素结合或由这些元素产生的因素，以及与这些元素的分离有关的因素。 灭火器所在地 这些实验应该有助于阐明分子的 调节哺乳动物细胞分化的机制。 的 实验也将有助于我们对生物学的了解， 黑素瘤细胞。 所获得的关于管理机制的信息可以 与肿瘤发生有关，因为恶性肿瘤（如分化）是 受到细胞杂交和BrdU的影响。

The long term goal of this research is to elucidate the molecular mechanisms by which differentiation is regulated in melanoma cells. The experiments will involve the techniques of somatic cell genetics (cell hybridization and gene transfer) and the use of the thymidine analog 5- bromodeoxyuridine (BrdU) in combination with the techniques of recombinant DNA. The specific aims of the research relate to the extinction of pigmentation in somatic cell hybrids, the transaction of the fibroblast tyrosinase gene in hybrids, and the suppression of pigmentation by BrdU. The experiments with cell hybrids will focus on the chromosomal localization of the regulatory element causing extinction, the identification of the extinguisher locus, the occurrence of transactivation, the identification of DNA sequences (presumably upstream) in the tyrosinase gene that are involved in regulation, and the analysis of the way in which these sequences affect gene expression. The experiments with BrdU will focus on the identification of DNA sequences in the tyrosinase gene that are involved in suppression, the analysis of the way in which these sequences act, and the determination of the role of BrdU in the interactions between regulatory factors and regulatory regions of the tyrosinase gene. These experiments should lead to the identification of cis- and trans-acting regulatory elements involved in the regulation of tyrosinase gene expression, to the identification of factors binding to or produced by these elements, and to the isolation of the extinguisher locus. These experiments should contribute to the elucidation of the molecular mechanisms regulating differentiation in mammalian cells. The experiments also will contribute to our knowledge of the biology of melanoma cells. The information gained about regulatory mechanisms could be relevant to tumorigenesis, since malignancy (like differentiation) is affected by cell hybridization and by BrdU.