HORMONAL REGULATION OF CULTURED PANCREATIC ACINAR CELLS

培养的胰腺腺泡细胞的激素调节

• 批准号: 3234187
• 负责人: Craig D Logsdon
• 金额: $ 16.41万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3234187
• 关键词: bombesin; calcium channel; cell growth regulation; cell population study; cholecystokinin; cyclic AMP; cytogenetics; eicosanoids; gene expression; growth inhibitors; hormone regulation /control mechanism; laboratory mouse; laboratory rat; pancreas; protein kinase C; protooncogene; radiotracer; second messengers; tissue /cell culture; transforming growth factors

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.

本研究的目的是阐明生理调节 胰腺腺泡细胞的生长。 我们建议利用体外模型， 表征胰腺腺泡细胞中涉及的细胞内机制 生长调节 需要体外模型，因为 调节生长的调节系统。 此外，体外模型 提供生物化学和分子生物学技术， 难以或不可能在体内使用。 在此之前，我们开发了一个主要的 对胆囊收缩素有营养反应的小鼠腺泡细胞的培养 （CCK）。 我们还开发了大鼠腺泡AR 42 J细胞作为生理模型， 线，其保留了对CCK的差异化反应。 本 建议，我们将追求三个主要目标：1）表征 胆囊收缩素（CCK）刺激的细胞内机制 腺泡细胞生长。 我们将研究PI水解，Ca 2+， 蛋白激酶C、类花生酸、cAMP和癌基因。 2)研究 通过转化生长因子-B（TGF-β）抑制腺泡细胞生长。 TGF-β在体外抑制胰腺腺泡细胞的生长，并可能与胰腺癌的发生有关。 在体内腺泡细胞生长的调节中起重要作用。 我们将 表征这种抑制作用，并研究细胞内 涉及的机制。 3)研究表达调控的 核癌基因c-fos、c-jun和c-myc与胰腺癌的关系 腺泡细胞生长。 我们将阐明潜在的机制， CCK和TGF-β对这些癌基因表达的影响， 其表达与腺泡细胞生长的相关性。 腺泡信息 细胞生长与胰腺疾病的理解有关 包括胰腺炎囊性纤维化和癌症