TRANSCRIPTIONAL REGULATION OF THE HUMAN N-CADERIN GENE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 钙粘附素是一种细胞黏附蛋白，参与黏附连接和桥粒的形成，构成细胞-细胞连接的跨膜成分。从上皮表型到侵袭性癌表型的转变与E-钙粘附素在许多组织和细胞系中的表达缺失有关。此外，它还与N-钙粘附素的新表达有关，N-钙粘附素是一种在上皮细胞中通常不表达的钙粘附素。事实上，在一些乳腺癌细胞系中，细胞运动性和侵袭性表型的增加与N-钙粘蛋白的表达直接相关，而不是与E-钙粘附素的丢失有关。鉴于N-钙粘蛋白在调节细胞运动和侵袭中的作用，我们正在转录水平上研究N-钙粘蛋白的表达调控。到目前为止，只对鸡的N-钙粘素基因进行了研究，这项工作只是初步评估。我们目前正在定位人类N-钙粘蛋白基因启动子和第一内含子中的DNase I超敏感部位，以确定调控该基因的转录因子的结合部位。我们还在测试荧光素酶报告结构，以评估这些超敏序列在体外的功能作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cadherins are cell adhesion proteins involved in adherens junctions and desmosomes and make up the transmembrane component of the cell-cell junctions. Transformation from an epithelial phenotype to an invasive cancerous phenotype has been linked with loss of E-cadherin expression in a number of tissues and cell lines. In addition it has been linked with new expression of N-cadherin, a cadherin not normally expressed in epithelial cells. In fact in some breast cancer cell lines an increase in cell motility and invasive phenotype is directly related to expression of N-cadherin rather than loss of E-cadherin. In light of the role for N-cadherin in mediating cell motility and invasiveness we are studying the regulation of N-cadherin expression at the transcriptional level. Only the chicken N-cadherin gene has been studied to date and that work was only a preliminary evaluation. We are currently mapping DNAse I hypersensitive sites in the promoter and first intron of the Human N-cadherin gene to identify binding sites for transcription factor that regulate this gene. We are also testing luciferase reporter constructs to evaluate the functional role of these hypersensitive sequences in vitro.