Increased expression of EGFR in gastric mucosa of aged rats.
Increased expression of EGFR in gastric mucosa of aged rats.
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老年大鼠胃粘膜EGFR表达增加。
DOI：
10.1152/ajpgi.1997.273.2.g389
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Majumdar,AP
中科院分区：
文献类型：
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作者：
Tureaud,J;Sarkar,FH;Fligiel,SE;Kulkarni,S;Jaszewski,R;Reddy,K;Yu,Y;Majumdar,AP
尽管在fisher -344大鼠中发现衰老与胃粘膜增殖活性增加有关，但对调节这一过程的细胞内事件知之甚少。本研究探讨了胃粘膜酪氨酸激酶活性和表皮生长因子受体（EGFR）及其结构和功能类似物p185c-erbB-2 （c-erbB-2/c-neu原癌基因的蛋白产物）表达的年龄相关变化。我们观察到，与4岁或12岁的大鼠相比，24岁大鼠胃粘膜的内在酪氨酸激酶活性和EGFR和p185c-erbB-2的酪氨酸磷酸化明显更高。这与EGFR蛋白水平升高以及EGFR和p185c-erbB-2的稳态mRNA水平升高有关。此外，我们还观察到老龄大鼠胃粘膜中转化生长因子- α （tgf - α， EGFR的主要配体之一）的稳态mRNA水平比4龄（幼龄）动物高3倍。与此同时，胃粘膜中tgf - α的18 kda前体形式的相对浓度增加了5倍，而细胞质中没有。总之，我们的数据表明，衰老与胃黏膜中EGFR和p185c-erbB-2酪氨酸激酶活性增加有关。此外，衰老导致胃粘膜中tgf - α积累增加的观察结果提出了一种可能性，即膜结合的tgf - α可能在一定程度上负责衰老大鼠胃粘膜中egfr诱导的组成性活性信号通路，进而刺激粘膜增殖活性。
Although in Fischer-344 rats aging is found to be associated with increased gastric mucosal proliferative activity, little is known about the intracellular events that regulate this process. The present investigation examines the age-related changes in gastric mucosal tyrosine kinase activity and expression of epidermal growth factor receptor(EGFR) and its structural and functional analog p185c-erbB-2, the protein product of c-erbB-2/c-neu protooncogene. We observed a significantly higher intrinsic tyrosine kinase activity and tyrosine phosphorylation of EGFR and p185c-erbB-2 in the gastric mucosa of 24-mo-old (aged) rats than in that of their 4- or 12-mo-old counterparts. This was associated with increased levels of EGFR protein and steady-state mRNA levels of EGFR and p185c-erbB-2. In addition, we also observed threefold higher steady-state mRNA levels of transforming growth factor-alpha (TGF-alpha; one of the primary ligands of EGFR) in the gastric mucosa of aged rats than in that of 4-mo-old (young) animals. This was accompanied by a fivefold increase in the relative concentration of the 18-kDa precursor form of TGF-alpha in gastric mucosal membranes but not in the cytosol. In conclusion, our data demonstrate that aging is associated with increased tyrosine kinase activity of EGFR and p185c-erbB-2 in the gastric mucosa. Moreover, the observation that aging results in increased accumulation of TGF-alpha in gastric mucosal membranes raises the possibility that the membrane-bound TGF-alpha could partly be responsible for the constitutively active EGFR-induced signaling pathway in the gastric mucosa of aged rats and, in turn, for stimulation of mucosal proliferative activity.