RPG: Regulation of Prolactin Gene Expression by Cell Contacts

垂体催乳素（PRL）基因表达的调控涉及许多神经递质、激素、生长因子和其他可溶性信号分子的作用。此外，细胞外基质成分的变化可以调节PRL基因的表达，调节PRL的药物也可以诱导细胞粘附性的变化。初步数据表明，PRL基因在大鼠垂体瘤235-1细胞中的表达是在形成大细胞聚集体的培养条件下诱导的，并且高PRL mRNA水平依赖于这些聚集体的存在。为了追求这些观察结果，拟议的研究将尝试：通过细胞培养研究确定PRL基因表达的诱导是否需要与聚集体接触，或者是否由聚集体产生可溶性因子并独立于细胞接触而起作用。如果信号似乎是一个可溶性因子，将检测聚集条件培养基诱导PRL mRNA的能力。2. 确定通过激动剂/抑制剂研究信号是否通过细胞激酶途径转导。肌动蛋白和微管蛋白染色将用于检查细胞骨架组织的变化。β -整合素、钙粘蛋白和神经细胞粘附分子的存在也将被确定。3. 确定PRL mRNA的增加是否发生在转录水平。这些研究将为进一步研究PRL基因的接触调控提供基础信息。＊＊＊

9507173 Delidow Regulation of pituitary prolactin (PRL) gene expression involves the actions of a number of neurotransmitters, hormones, growth factors and other soluble signaling molecules. In addition it has been shown that changes in extracellular matrix components can regulate PRL gene expression, and that agents which regulate PRL can also induce changes in cell adhesiveness. Preliminary data has shown that PRL gene expression in the rat pituitary tumor 235-1 cells is induces under culture conditions in which large cell aggregates form, and that high PRL mRNA levels are dependent upon the presence of these aggregates. To persue these observations, the proposed research will attempt to: 1. Determine by cell culture studies whether induction of PRL gene expression requires contact with aggregates, or whether a soluble factor(s) is produced by aggregates and acts independently of cell contact. If the signal appears to be a soluble factor, aggregate-conditioned media will be assayed for the ability to induce PRL mRNA. 2. Determine by agonist/inhibitor studies whether the signal is transduced via cellular kinase pathways. Actin and tubulin staining will be used to examine changes in cytoskeletal organization. The presence of beta1-integrins, cadherins and neural cell adhesion molecules will also be determined. 3. Determine whether the increase in PRL mRNA occurs at the transcriptional level. These studies will provide a base of information for future studies on contact regulation of PRL gene expression. ***