Neurotensin-mediated activation of MAPK pathways and AP-1 binding in the human pancreatic cancer cell line, MIA PaCa-2
Neurotensin-mediated activation of MAPK pathways and AP-1 binding in the human pancreatic cancer cell line, MIA PaCa-2
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DOI：
10.1006/bbrc.2000.2335
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发表时间：
2000-03-24
影响因子：
3.1
通讯作者：
Evers, BM
中科院分区：
文献类型：
--
作者：
Ehlers, RA;Zhang, YJ;Evers, BM
神经降压素（NT）是一种胃肠道（GI）激素，与其受体（NTR）结合刺激正常和肿瘤性GI组织的增殖;其分子机制在很大程度上仍不清楚。有丝分裂原活化蛋白激酶（MAPK）是一类细胞内激酶家族，其通过易位至细胞核并激活转录因子来传递促有丝分裂信号。本研究的目的是：（1）鉴定NT是否激活MAPK（ERK 1/2和JNK）;（2）使用具有高亲和力NTR的人胰腺癌细胞系MIA PaCa-2来确定NT对下游转录因子的影响。ERK和JNK活性在3-6分钟内刺激NT（10 nM）处理; ERK和JNK蛋白的稳态水平不变。此外，NT处理导致AP-1结合活性增加，如通过凝胶位移分析所确定的。描述调节NT的细胞效应的信号转导机制将为负责NT介导的对正常细胞和肿瘤细胞的效应的分子途径提供重要的见解，（C）2000学术出版社。
Neurotensin (NT), a gastrointestinal (GI) hormone, binds its receptor (NTR) to stimulate proliferation of normal and neoplastic GI tissues; the molecular mechanisms remain largely undefined. Mitogen-activated protein kinases (MAPKs) are a family of intracellular kinases that transmit mitogenic signals by translocating to the nucleus and activating transcription factors. The purposes of this study were: (1) to identify whether the MAPKs (ERK1/2 and JNK) are activated by NT and (2) to determine the effect of NT on downstream transcription factors using the human pancreatic adenocarcinoma cell line, MIA PaCa-2, which possesses high-affinity NTR. Both ERK and JNK activity were stimulated within 3-6 min by treatment with NT (10 nM); steady-state levels of ERK and JNK protein were unchanged. Moreover, NT treatment resulted in increased AP-1 binding activity as determined by gel shift analysis. Delineating the signal transduction mechanisms regulating the cellular effects of NT will provide important insights into the molecular pathways responsible for NT-mediated effects on both normal and neoplastic cells, (C) 2000 Academic Press.