Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

90 primary breast carcinomas and 18 metastases were immunostained for c-erbB-2 protein and neuron specific enolase. 30 tumours were c-erbB-2 negative and NSE positive, 23 tumours were NSE negative and c-erbB-2 positive. 1 tumour expressed focal immunoreactivity for both markers. 54 of the 108 tumours (50%) did not express either marker. Hormone immunoreactivity was present in single cells and in small groups of cells in 18 of the 31 NSE positive tumours. Bombesin, neurotensin and prealbumin were present in 4 cases each, followed by beta-endorphin and VIP in 3 cases each, leu-enkephalin in 2 cases and gastrin, serotonin, substance P, glucagon and somatostatin in 1 case each. None of 10 NSE negative breast carcinomas were comprised of cells expressing immunoreactivity for hormones. By immunoelectron microscopic examination the c-erbB-2 protein was shown to be present on the cell membrane, on smooth areas, microvilli and in coated pits. Immunoreactivity was also expressed in vesicles in cytoplasm and along rough endoplasmic reticulum. The study shows that c-erbB-2 protein expression and neuroendocrine activity are present in different tumour cell populations. This supports the hypothesis that the presence of c-erbB-2 protein, indicating an elevated cellular tyrosine kinase activity with stimulation of growth, intracellular Ca++, and phosphatidylinositol derivates, means that the same cell does not need regulation of the same factors by stimulation of peptide hormone receptors. Thus the production of autocrine and paracrine factors is switched off.
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PMID:C-erbB-2 protein and neuroendocrine expression in breast carcinomas. 167 29

Substance P is a member of the tachykinin family of neuropeptides that plays an important role in pain transmission, neurogenic inflammatory diseases and the adaptive response to stress. Substance P exerts its biological activities via binding to a G-protein coupled receptor of the neurokinin (NK) receptor family. Here, we show by Western blot experiments that substance P induced a transient synthesis of the zinc finger transcriptional regulator Egr-1 in human glioma cells. Substance P-induced stimulation of Egr-1 biosynthesis was completely inhibited by the mitogen-activated protein kinase kinase inhibitor PD98059 and by AG1487, an epidermal growth factor (EGF) receptor-specific tyrosine kinase inhibitor. These results indicate that transactivation of the EGF receptor as well as stimulation of the mitogen activated/extracellular signal-regulated protein kinase (ERK) are essential for substance P/NK-1 receptor-induced activation of Egr-1 biosynthesis. Moreover, we show that the signaling cascade initiated by substance P or EGF are indistinguishable, including the activation of the EGF receptor, the activation of ERK, and the final stimulation of Egr-1 biosynthesis. The synthesis of Egr-1 in glioma cells as a result of substance P stimulation suggests that substance P exerts long-term effects in glioma cells via Egr-1-mediated gene transcription.
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PMID:Substance P induced biosynthesis of the zinc finger transcription factor Egr-1 in human glioma cells requires activation of the epidermal growth factor receptor and of extracellular signal-regulated protein kinase. 1238 23

Substance P (SP) participates in acute intestinal inflammation via binding to the G-protein-coupled neurokinin-1 receptor (NK-1R) and release of proinflammatory cytokines from colonic epithelial cells. SP also stimulates cell proliferation, a critical event in tissue healing during chronic colitis, via transactivation of the epidermal growth factor (EGF) receptor (EGFR) and activation of mitogen-activated protein kinase (MAPK). Here we examined the mechanism by which SP induces EGFR and MAPK activation. We used non-transformed human NCM460 colonocytes stably transfected with the human NK-1R (NCM460-NK-1R cells) as well as untransfected U373 MG cells expressing high levels of endogenous NK-1R. Exposure of both cell lines to SP (10(-7) m) stimulated EGFR activation (1 min) followed by extracellular signal-regulated protein kinase (ERK1/2) activation (2-5 min). SP-induced ERK1/2 activation was blocked by pretreatment with the metalloproteinase inhibitor Batimastat/GM6001, the EGFR phosphorylation inhibitor AG1478, and the tumor necrosis factor-alpha-converting enzyme (TACE) inhibitor TAPI-1. Pretreatment with antibodies against potential EGFR ligands suggested that transforming growth factor-alpha (TGFalpha), but not the other EGFR ligands EGF, heparin-binding EGF, or amphiregulin, mediates SP-induced EGFR transactivation. SP stimulated TGFalpha release into the extracellular space that was measurable within 2 min, and this release was inhibited by metalloproteinase inhibitors and the TACE inhibitor TAPI-1. SP also induced MAPK-mediated cell proliferation that was inhibited by TACE, matrix metalloproteinase (MMP), EGFR, and MEK1 inhibitors. Thus, in human colonocytes, NK-1R-induced EGFR and MAPK activation and cell proliferation involve matrix metalloproteinases (most likely TACE) and the release of TGFalpha. These signaling mechanisms may be involved in the protective effects of NK-1R in chronic colitis.
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PMID:Metalloproteinases and transforming growth factor-alpha mediate substance P-induced mitogen-activated protein kinase activation and proliferation in human colonocytes. 1531 41