RPG: Regulation of Prolactin Gene Expression by Cell Contacts

9507173垂体催乳素(PRL)基因表达的Delidow调节涉及多种神经递质、激素、生长因子和其他可溶性信号分子的作用。此外，已有研究表明，细胞外基质成分的改变可以调节PRL基因的表达，调节PRL的药物也可以诱导细胞黏附的变化。初步研究表明，大鼠垂体瘤235-1细胞中PRL基因的表达是在大细胞聚集体形成的培养条件下诱导的，高水平的PRL基因表达依赖于这些聚集体的存在。为了证明这些观察结果，建议的研究将试图：1.通过细胞培养研究确定催乳素基因表达的诱导是否需要与聚集体接触，或者可溶性因子(S)是否由聚集体产生并独立于细胞接触而起作用。如果信号看起来是一个可溶的因素，聚集条件培养液将被检测诱导PRL mRNA的能力。2.通过激动剂/抑制物研究信号是否通过细胞激动剂/抑制物转导。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。β1整合素、钙粘附素和神经细胞黏附分子的存在也将被确定。3.确定PRL基因表达的增加是否发生在转录水平。这些研究将为今后研究PRL基因表达的接触性调控提供信息基础。***

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. ***