Hägg Maria, Liljegren Asa, Carlsson Jörgen, Rönnstrand Lars, Lennartsson Johan
Ludwig Institute for Cancer Research, Biomedical Center, SE-751 24 Uppsala, Sweden.
Int J Mol Med. 2002 Nov;10(5):655-9.
Dextran-conjugated EGF (EGF-dextran) has a potential use for targeted radionuclide therapy of tumors that overexpress the epidermal growth factor receptor (EGFR). There are plans to treat both bladder carcinomas and malignant gliomas with local injections of radiolabeled EGF-dextran since these tumors often express high levels of EGFR. In this report we show that EGF and EGF-dextran differentially activate the EGFR. In the human glioma cell line U-343, activation of the serine/threonine kinases Erk and Akt is identical upon stimulation with EGF or EGF-dextran. However, the effect on phospholipase Cgamma1 (PLCgamma1) phosphorylation differs. In cells stimulated with EGF-dextran, the PLCgamma1 phosphorylation is lower than in cells stimulated with EGF. This observation could be explained by the fact that the PLCgamma1 association sites in the EGFR, tyrosine residues 992 and 1173, were phosphorylated to a lower degree when the receptor was stimulated with EGF-dextran as compared to with EGF.
葡聚糖偶联表皮生长因子（EGF-葡聚糖）在对过表达表皮生长因子受体（EGFR）的肿瘤进行靶向放射性核素治疗方面具有潜在用途。由于膀胱癌和恶性胶质瘤通常高表达EGFR，因此计划通过局部注射放射性标记的EGF-葡聚糖来治疗这两种肿瘤。在本报告中，我们表明EGF和EGF-葡聚糖对EGFR的激活作用存在差异。在人胶质瘤细胞系U-343中，用EGF或EGF-葡聚糖刺激后，丝氨酸/苏氨酸激酶Erk和Akt的激活情况相同。然而，对磷脂酶Cγ1（PLCγ1）磷酸化的影响有所不同。在用EGF-葡聚糖刺激的细胞中，PLCγ1的磷酸化水平低于用EGF刺激的细胞。这一现象可以通过以下事实来解释：与用EGF刺激相比，当用EGF-葡聚糖刺激受体时，EGFR中PLCγ1的结合位点（酪氨酸残基992和1173）的磷酸化程度较低。
