Helicobacter pylori activates mitogen-activated protein kinase cascades and induces expression of the proto-oncogenes c-fos and c-jun
Helicobacter pylori activates mitogen-activated protein kinase cascades and induces expression of the proto-oncogenes c-fos and c-jun
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DOI：
10.1074/jbc.m000959200
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发表时间：
2000-05-26
影响因子：
4.8
通讯作者：
Pahl, HL
中科院分区：
文献类型：
--
作者：
Meyer-ter-Vehn, T;Covacci, A;Pahl, HL
幽门螺杆菌是粘膜相关淋巴组织淋巴瘤和胃腺癌的致病因子。感染H.与未感染的个体相比，幽门螺杆菌感染者患癌症的风险增加3-6倍。H.表达细胞毒素相关抗原A（CagA）的幽门螺杆菌菌株比CagA阴性菌株更常与肿瘤形成相关。然而，幽门螺杆菌引起肿瘤转化的分子机制仍不清楚。在这里，我们报告了胃上皮细胞暴露于H。pylori诱导转录因子激活蛋白1的激活，强烈诱导原癌基因c-fos和c-jun的激活。我们证明了H. pylori激活ERK/MAP激酶级联，导致Elk-1磷酸化和c-fos转录增加。a.不表达CagA或由CagI致病岛编码的cog基因突变的幽门螺杆菌菌株不诱导激活蛋白1、MAP激酶活性或c-fos或c-jun激活。原癌基因的激活可能是H. pylori诱发的肿瘤。
Helicobacter pylori is an etiological agent in the development of mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma. Patients infected with H. pylori carry a 3-6-fold increased risk of developing cancer compared with uninfected individuals. H. pylori strains expressing the cytotoxin-associated antigen A (CagA) are more frequently associated with the development of neoplasia than cagA-negative strains. However, the molecular mechanism by which H, pylori causes neoplastic transformation remains unclear. Here we report that exposure of gastric epithelial cells to H. pylori induces activation of the transcription factor activator protein 1, Activation of the proto-oncogenes c-fos and c-jun is strongly induced. We show that H. pylori activates the ERK/MAP kinase cascade, resulting in Elk-l phosphorylation and increased c-fos transcription. a. pylori strains that do not express CagA or that are mutated in cog genes encoded by the CagI pathogenicity island do not induce activator protein 1, MAP kinase activity, or c-fos or c-jun activation. Proto-oncogene activation may represent a crucial step in the pathomechanism of H. pylori induced neoplasia.