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he study on the anti-tumor effects of human epidermal growth factor

人表皮生长因子抗肿瘤作用的研究

基本信息

批准号：
04670726
负责人：
MURAYAMA Yoichi
金额：
$ 1.34万
依托单位：
TOKYO MEDICAL AND DENTAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

High concentration of epidermal growth factor(EGF) suppressed the tumor growth of human breast cancer, esophageal cancer, gastric cancer, and colonic carcinoma transplanted into nude mice. The effects were dose dependent. We studied on the mechanism of growth-inhibitory effect of human recombinant EGF on these tumors and discovered several important mechanisms using the methods of molecular cellular biology. We also found a novel signal transduction of EGF.Results of our investigations are follow :1. High concentration of EGF induced incresed expression of EGF receptor(EGFR). However, EGF binding function of EGFR was extreamingly decreased.2. High concentration of EGF induced the down regulation of intracellular cAMP synthesis.3. High concentrations of EGF induced the accumulation of P^<53>. This phenomenon was responsive to the levels of cAMP.4. EGF induced wild type P^<53> functions as anti-ras and anti-fos.5. The mutant P^<53> at codon 181(C to T transiversions) was wildtype phenotype.6. High concentration of EGF induced P^<53> dependent apoptosis.7. TGF-beta regulates cell cycle progression through P^<53>.In conclusions, the indicated mechanism from our results are follows : Decreased EGF binding function of EGFR -> Down-regulation of cAMP synthesis -> Production of P^<53> expression -> P^<53> dependent apoptosis or Down-regulation of ras and fos gene induced by P^<53>.We also discovered a novel signal transduction of EGF mediated through P^<53> gene, BAX gene, and bcl-2 gene which induces apoptosis.

高浓度表皮生长因子（EGF）可抑制人乳腺癌、食管癌、胃癌、结肠癌移植裸鼠的肿瘤生长。效果是剂量依赖性的。我们利用分子细胞生物学的方法研究了人重组EGF对这些肿瘤生长抑制作用的机制，发现了一些重要的机制。我们还发现了一种新的EGF信号转导。我们的调查结果如下：高浓度EGF诱导EGF受体（EGFR）表达增加。然而，EGFR的EGF结合功能却大大降低。高浓度EGF诱导细胞内cAMP合成下调。高浓度EGF诱导P^<53>的积累。这一现象与camp的水平有关。EGF诱导的野生型P^<53>具有抗ras和抗fo0的功能。突变体P^<53>在密码子181（C到T过渡）为野生型表型。高浓度EGF诱导P^<53>依赖性细胞凋亡。tgf - β通过P^<53 bb0调控细胞周期进程。综上所述，我们的结果提示的机制如下：EGFR ->的EGF结合功能降低下调cAMP合成->产生P^<53>表达-> P^<53>依赖性凋亡或P^<53>诱导ras和fos基因下调。我们还发现了一种通过P^<53>基因、BAX基因和bcl-2基因介导的EGF诱导细胞凋亡的新信号转导。