HORMONAL REGULATION OF CULTURED PANCREATIC ACINAR CELLS

本研究的目的是阐明其生理调节机制。 胰腺腺泡细胞的生长。我们建议利用体外模型来 胰腺腺泡细胞参与的细胞内机制 生长调控。由于体外模型的复杂性，需要建立体外模型。 调控增长的监管体系。此外，体外模型 提供符合以下条件的生化和分子生物学技术 难以或不可能在体内使用的。之前，我们开发了一种主要的 小鼠腺泡细胞对胆囊收缩素营养反应的培养 (CCK)。我们还建立了大鼠腺泡细胞AR42J的生理模型 LINE，它保留了对CCK的差异反应。在现在 建议，我们将追求三个主要目标：1)描述 CCK刺激血管内皮细胞的细胞内机制 腺泡细胞生长。我们将研究PI水解酶、钙离子、 蛋白激酶C，二十碳五烯酸，环磷酸腺苷和癌基因。2)研究 转化生长因子-B对腺泡细胞生长的抑制作用 转化生长因子-β抑制体外培养的胰腺腺泡细胞生长 在体内调节腺泡细胞生长中的重要作用。我们会 表征这种抑制作用，并研究细胞内 涉及的机制。3)研究细胞因子的表达调控。 核癌基因c-fos、c-jun和c-myc及其与胰腺的相关性 腺泡细胞生长。我们将阐明潜在的机制 CCK和转化生长因子-β对上述癌基因表达的影响及意义 它们的表达与腺泡细胞生长的相关性。关于阿森纳的信息 细胞生长与胰腺疾病的认识有关 包括胰腺炎、囊性纤维化和癌症。

The objective of this research is to elucidate the physiologic regulation of pancreatic acinar cell growth. We propose to utilize in vitro models to characterize intracellular mechanisms involved in pancreatic acinar cell growth regulation. In vitro models are required due to the complexity of the regulatory systems modulating growth. Furthermore, in vitro models make available biochemical and molecular biological techniques that are difficult or impossible to use in vivo. Previously, we developed a primary culture of mouse acinar cells which responds trophically to cholecystokinin (CCK). We also developed as a physiologic model the rat acinar AR42J cell line, which retains differentiated responses to CCK. In the present proposal, we will pursue three major aims: 1) Characterize the intracellular mechanisms involved in cholecystokinin (CCK) stimulation of acinar cell growth. We will investigate the roles of PI hydrolysis, Ca2+, protein kinase C, eicosinoids, cAMP, and oncogenes. 2) Study the inhibition of acinar cell growth by transforming growth factor-B (TGF-B). TGF-B inhibits pancreatic acinar cell growth in vitro and may have an important role in the regulation of acinar cell growth in vivo. We will characterize this inhibitory action and investigate the intracellular mechanisms involved. 3) Investigate the regulation of expression of the nuclear oncogenes c-fos, c-jun, and c-myc and their relevance to pancreatic acinar cell growth. We will elucidate the mechanisms underlying the effects of CCK and TGF-B on the expression of these oncogenes and the relevance of their expression on acinar cell growth. Information on acinar cell growth is relevant to the understanding of pancreatic diseases including pancreatitis, cystic fibrosis, and cancer.