TRANSCRIPTIONAL REGULATION OF THE HUMAN N-CADERIN GENE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。钙粘蛋白是参与粘附连接和桥粒的细胞粘附蛋白，并且构成细胞-细胞连接的跨膜组分。从上皮表型到侵袭性癌表型的转化与许多组织和细胞系中E-钙粘蛋白表达的丧失有关。此外，它与N-钙粘蛋白的新表达有关，N-钙粘蛋白是一种在上皮细胞中通常不表达的钙粘蛋白。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E-钙粘蛋白的丢失。鉴于N-钙粘蛋白在介导细胞运动和侵袭中的作用，我们正在研究N-钙粘蛋白在转录水平上的表达调控。迄今为止，只有鸡N-钙粘蛋白基因被研究，这项工作只是初步评估。我们目前正在绘制DNA酶I超敏位点的启动子和人类N-钙粘蛋白基因的第一个内含子，以确定转录因子调节该基因的结合位点。我们也在测试荧光素酶报告基因构建体，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.