Neurotensin-mediated activation of MAPK pathways and AP-1 binding in the human pancreatic cancer cell line, MIA PaCa-2

被引:60
作者
Ehlers, RA [1 ]
Zhang, YJ [1 ]
Hellmich, MR [1 ]
Evers, BM [1 ]
机构
[1] Univ Texas, Med Branch, Dept Surg, Galveston, TX 77555 USA
关键词
neurotensin; G-protein receptor; MAPK; AP-1; signal transduction; gut hormone;
D O I
10.1006/bbrc.2000.2335
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:704 / 708
页数:5
相关论文
共 53 条
  • [11] Ehlers RA, 1998, SURGERY, V124, P239, DOI 10.1016/S0039-6060(98)70126-6
  • [12] EHLERS RA, 2000, IN PRESS ANN SURG
  • [13] NEUROTENSIN STIMULATES GROWTH OF COLONIC MUCOSA IN YOUNG AND AGED RATS
    EVERS, BM
    IZUKURA, M
    CHUNG, DH
    PAREKH, D
    YOSHINAGA, K
    GREELEY, GH
    UCHIDA, T
    TOWNSEND, CM
    THOMPSON, JC
    [J]. GASTROENTEROLOGY, 1992, 103 (01) : 86 - 91
  • [14] NEUROTENSIN PREVENTS INTESTINAL MUCOSAL HYPOPLASIA IN RATS FED AN ELEMENTAL DIET
    EVERS, BM
    IZUKURA, M
    TOWNSEND, CM
    UCHIDA, T
    THOMPSON, JC
    [J]. DIGESTIVE DISEASES AND SCIENCES, 1992, 37 (03) : 426 - 431
  • [15] EVERS BM, 1995, MOL CELL BIOL, V15, P3870
  • [16] NEUROTENSIN EXPRESSION AND RELEASE IN HUMAN COLON CANCERS
    EVERS, BM
    ISHIZUKA, J
    CHUNG, DH
    TOWNSEND, CM
    THOMPSON, JC
    [J]. ANNALS OF SURGERY, 1992, 216 (04) : 423 - 431
  • [17] EVERS BM, 1999, GASTROINTESTINAL END
  • [18] NEUROTENSIN INDUCES HYPERPLASIA OF THE PANCREAS AND GROWTH OF THE GASTRIC ANTRUM IN RATS
    FEURLE, GE
    MULLER, B
    RIX, E
    [J]. GUT, 1987, 28 : 19 - 23
  • [19] NEUROTENSIN STIMULATES FORMATION OF CYCLIC-GMP IN MURINE NEURO-BLASTOMA CLONE N1E-115
    GILBERT, JA
    RICHELSON, E
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1984, 99 (2-3) : 245 - 246
  • [20] Interleukin-1-induced nuclear factor-κB-IκBα autoregulatory feedback loop in hepatocytes -: A role for protein kinase Cα in post-transcriptional regulation of IκBα resynthesis
    Han, YQ
    Meng, T
    Murray, NR
    Field, AP
    Brasier, AR
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (02) : 939 - 947