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

高浓度表皮生长因子（EGF）抑制人乳腺癌、食道癌、胃癌、结肠癌裸鼠移植瘤的生长。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对这些肿瘤的生长抑制作用的机制，并发现了几个重要的机制。我们还发现了一种新的EGF信号转导机制。我们的研究结果如下： 1．高浓度的EGF诱导EGF受体(EGFR)表达增加。但EGFR与EGF的结合功能急剧下降。2．高浓度EGF诱导细胞内cAMP合成下调。 3．高浓度的EGF诱导P^53的积累。这种现象对 cAMP.4 的水平有反应。 EGF诱导的野生型P^ 53 起到抗ras和抗fos.5的作用。密码子181处的突变体P^<53>(C至T转换)为野生型表型。6．高浓度EGF诱导P^53依赖性细胞凋亡。7． TGF-β通过P^<53>调节细胞周期进程。总之，我们的结果表明的机制如下：EGFR的EGF结合功能降低 -> cAMP合成下调 -> P^<53>表达的产生 -> P^<53>依赖性细胞凋亡或P^<53>诱导的ras和fos基因下调。我们还发现了通过P^<53>基因介导的EGF新信号转导， BAX基因和诱导细胞凋亡的bcl-2基因。

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.