Expression of EGF-receptor related protein (ERRP) decreases in gastric mucosa during aging and carcinogenesis.
Expression of EGF-receptor related protein (ERRP) decreases in gastric mucosa during aging and carcinogenesis.
复制标题
在衰老和癌变过程中，胃粘膜中 EGF 受体相关蛋白 (ERRP) 的表达降低。
DOI：
10.1023/a:1023078924686
复制
发表时间：
2003
影响因子：
3.1
通讯作者：
Sarkar,FazlulH
中科院分区：
文献类型：
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作者：
Majumdar,AdhipPN;Du,Jianhua;Hatfield,JamesS;Levi,Edi;Adsay,Volkan;Schmelz,EvaM;Nagothu,KiranK;Jaszewski,Richard;Kucuk,Omer;Sarkar,FazlulH
衰老和胃肠道恶性肿瘤，包括胃部肿瘤，与表皮生长因子受体(EGFR)的激活有关。虽然调控这一过程的细胞内事件尚不清楚，但我们假设ERRP(EGFR相关蛋白；GenBank登录号AF187818)的丢失可能与这一事件有关。ERRP是最近发现的一种EGFR的负调控因子，与EGFR的配体结合胞外结构域具有很高的同源性。为了支持我们的假设，我们观察到在Fischer-344大鼠中，尽管衰老与胃粘膜中EGFR的激活增加有关，但在此期间ERRP在该组织中的表达减少。后者伴随着与ERRP结合的转化生长因子-α的数量的减少。与之相反，老年大鼠胃粘膜中与表皮生长因子受体结合的转化生长因子-α的量高于青年大鼠。伴随而来的是EGFR水平的升高。在胃粘膜中，EGFR和ERRP共存。与良性组织相比，人类胃腺癌中ERRP的表达显著降低，这已被证明与EGFR的激活有关。我们的结论是，在衰老和癌变过程中，胃粘膜中EGFR的激活增加可能部分是由于ERRP的缺失。
Aging and gastrointestinal malignancies, including that of the stomach are associated with increased activation of EGF-receptor (EGFR). Although the intracellular events that regulate this process are poorly understood, we hypothesize that loss of ERRP (EGFR-related protein; GenBank accession number AF187818), a recently identified negative regulator of EGFR, that possesses a substantial homology to the ligand binding extracellular domain of EGFR, may contribute to this event. In support of our hypothesis, we have observed that in Fischer-344 rats, whereas aging is associated with increased activation of EGFR in the gastric mucosa, expression of ERRP decreases in this tissue during this period. The latter is accompanied by a concomitant reduction in the amount of TGF-α bound to ERRP. In contrast, the amount of TGF-α bound to EGFR is found to be higher in the gastric mucosa of aged than in young rats. This is accompanied by a concomitant rise in EGFR levels. In the gastric mucosa, EGFR and ERRP are found to be colocalized. Gastric adenocarcinoma in humans, which has been shown to be associated with increased activation of EGFR, shows a substantial reduction in ERRP expression, when compared with benign tissues. We conclude that increased activation of EGFR in the gastric mucosa during aging and carcinogenesis may partly be due to the loss of ERRP.