REGULATION OF EGF RECEPTORS BY CALCIOTROPIC HORMONES

促钙激素对 EGF 受体的调节

• 批准号: 2518542
• 负责人: ESTHER A GONZALEZ
• 金额: $ 10.44万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-21 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2518542
• 关键词: 1,25 dihydroxycholecalciferol; RNase protection assay; cyclic AMP; epidermal growth factor; gene expression; genetic promoter element; growth factor receptors; hormone regulation /control mechanism; intermolecular interaction; messenger RNA; northern blottings; osteoblasts; parathyroid hormones; receptor binding; receptor expression; retinoate; tissue /cell culture

DESCRIPTION (Adapted from the Applicant's Abstract): This is a new application for a FIRST Award which proposes to study the regulation of EGF receptor expression in UMR rat osteoblast-like cells by PTH, calcitriol, and retinoic acid. Preliminary data indicates that PTH and calcitriol increase EGF binding and responses in UMR cells, and that this effect appears to be due to an increase in EGF receptor number rather than a change in binding affinity. Further analyses with Northern blot and RNase protection assays demonstrate that both agents induce an increase in steady state EGF receptor mRNA levels by 3 to 5-fold. Preliminary data using EGF receptor promoter constructs linked to a luciferase reporter gene demonstrate that these effects are likely transcriptional in nature. Retinoic acid alone also increased EGF binding, but blunted the effects of PTH and calcitriol on EGF binding. The hypotheses are that PTH, calcitriol, and retinoic acid all increase transcriptional rates of the EGF receptor, that retinoic acid interferes with PTH-stimulated cAMP production, and that retinoic acid modulates the effects of vitamin D on a putative VDRE in the 5' flanking region of the EGF receptor gene. The current proposal will explore in more detail the molecular basis of the effects of calciotropic hormones on EGF receptor expression. The Specific Aims are: 1) to determine the mechanism for the increase in EGF receptor mRNA in response to PTH, calcitriol, and retinoic acid; 2) to identify the regions in the EGF receptor promoter which are responsible for the actions of PTH, calcitriol, and retinoic acid on transcription; 3) to define the mechanism of interaction of calcitriol with retinoic acid; and 4) to investigate the mechanism of interaction of retinoic acid and PTH.

描述（改编自申请人摘要）：这是一个新的