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

高浓度的表皮生长因子（EGF）对人乳腺癌、食管癌、胃癌和结肠癌裸鼠移植瘤的生长有抑制作用。这些效应具有剂量依赖性。本研究应用分子细胞生物学方法对重组人表皮生长因子（EGF）抑制肿瘤生长的机制进行了研究，发现了几种重要的作用机制。我们还发现了一种新的EGF信号转导途径。高浓度EGF可诱导表皮生长因子受体（EGFR）表达增加。然而，EGFR的EGF结合功能却急剧下降。2.高浓度EGF诱导细胞内cAMP合成下调.高浓度的EGF可诱导P2的积累<53>。这种现象是响应cAMP的水平。4. EGF诱导的野生型P1<53>具有抗ras和抗fos的功能。密码子181处的突变体P^<53>（C至T转换）为野生型表型。高浓度的EGF诱导了P2<53>依赖性凋亡。TGF-β通过P^调控细胞周期进程<53>，其作用机制为：EGFR与EGF结合功能降低→ cAMP合成下调→ P^<53>表达增加→ P^<53>依赖性凋亡或P^诱导ras、fos基因下调<53>。我们还发现了一种新的EGF信号转导途径，即P^<53>基因、BAX基因和bcl-2基因介导的EGF诱导细胞凋亡。

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.