Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extracellularly applied ATP, UTP and UDP induce a transient increase in the intracellular Ca2+ concentration of mammary cells via a P2U receptor. The P2U receptor in the mammary tumor cell line MMT060562 was cloned and expressed in the human leukemia cell line K-562. The deduced amino acid sequence of the mammary tumor cell P2U receptor was 98% homologous with that of mouse NG108-15 cells. It was a member of the superfamily of GTP-binding-protein-coupled receptors. ATP and UTP induced the increase in the intracellular concentrations of Ca2+ and inositol-1,4,5-trisphosphate in both mammary tumor cells and P2U-receptor-expressed K562 cells. Dose-response curves on the production of inositol-1,4,5-trisphosphate and Ca2+ by ATP and UTP were consistently similar. Injection of GTP enhanced the ATP-induced outward current and injection of GTP gamma S induced a repetitive outward current. Both pertussis and cholera toxins did not affect ATP-induced calcium increase. It was suggested that the P2U receptor coupled with pertussis- and cholera-toxin-insensitive GTP-binding proteins and activated phosphoinositide turnover.
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PMID:Expression cloning and signal transduction pathway of P2U receptor in mammary tumor cells. 873 19

The respective production of specific immunoglobulin (Ig)G2a or IgG1 within 5 d of primary immunization with Swiss type mouse mammary tumor virus [MMTV(SW)] or haptenated protein provides a model for the development of T helper 1 (Th1) and Th2 responses. The antibody-producing cells arise from cognate T cell B cell interaction, revealed by the respective induction of Cgamma2a and Cgamma1 switch transcript production, on the third day after immunization. T cell proliferation and upregulation of mRNA for interferon gamma in response to MMTV(SW) and interleukin 4 in response to haptenated protein also starts during this day. It follows that there is minimal delay in these responses between T cell priming and the onset of cognate interaction between T and B cells leading to class switching and exponential growth. The Th1 or Th2 profile is at least partially established at the time of the first cognate T cell interaction with B cells in the T zone. The addition of killed Bordetella pertussis to the hapten-protein induces nonhapten-specific IgG2a and IgG1 plasma cells, whereas the anti-hapten response continues to be IgG1 dominated. This indicates that a Th2 response to hapten-protein can proceed in a node where there is substantial Th1 activity.
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PMID:T helper 1 (Th1) and Th2 characteristics start to develop during T cell priming and are associated with an immediate ability to induce immunoglobulin class switching. 954 31

The collagen-induced phosphorylation of discoidin domain receptor 1 (DDR1) in Wnt-5a-expressing HB2 mammary cells was effectively inhibited by pertussis toxin, but not by cholera toxin or antibodies blocking beta(1) integrins. Moreover, pertussis toxin reduced adhesion of the cells to collagen by approximately 50%, and antibodies against beta(1) integrins had a similar effect that was in fact additive to that of pertussis toxin. Cholera toxin had accordingly no such effect on adhesion. By comparison, pertussis toxin did not influence adhesion of Wnt-5a-antisense HB2 cells or MCF-7 mammary tumor cells, neither of which express Wnt-5a or exhibit activation of DDR1. In accordance with these results, direct mastoparan-induced activation of G-proteins in Wnt-5a-deficient MCF-7 cells enabled collagen-induced phosphorylation of DDR1 and enhanced their adhesion. The inactive analogue mastoparan-17 had no such effects on MCF-7 cells nor did active mastoparan affect adhesion of Wnt-5a-expressing HB2 cells. A possible explanation for how DDR1, a receptor tyrosine kinase (RTK), potentiates mammary cell adhesion comes from our observations that pertussis toxin also inhibited the recruitment of the cytoskeletal regulator phosphatidylinositol 3-kinase (PI3K) to DDR1 as well as its phosphorylation/activation. In accordance with that, the PI3K inhibitor wortmannin significantly impaired adhesion of normal Wnt-5a-expressing HB2 cells but had little effect on adhesion of Wnt-5a-antisense HB2 cells. Thus, a G(i/o)-protein signaling pathway mediates the effect of Wnt-5a expression by enabling collagen-induced activation of DDR1, which, in parallel with beta(1) integrins, regulates adhesion of mammary cells.
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PMID:Wnt-5a and G-protein signaling are required for collagen-induced DDR1 receptor activation and normal mammary cell adhesion. 1247 17

We have studied the role of endothelins (ET-1, ET-2 and ET-3) and ET receptors (ET-RA and ET-RB) in the invasive capacity of breast tumor cells, which express ET-1 and ET-2 as well as ET-RA and ET-RB. Of five human breast tumor cell lines tested, all expressed mRNAs for ET-1, ET-2, and ET-RB. ET-RA mRNA was expressed by four of five tumor cell lines. Breast tumor cells migrated toward ET-1 and ET-2 but not toward ET-3. Chemotaxis involved signaling via both receptors, and a pertussis toxin-sensitive p42/p44 mitogen-activated protein kinase (MAPK)-mediated pathway that could be inhibited by MAPK kinase (MEK)1/2 antagonists. Chemotaxis toward ETs did not involve p38 or stress-activated protein kinase (SAPK)/Jun N-terminal kinase (JNK) and was not inhibited by hypoxia. Incubation of tumor cells with ET-2 also increased chemotaxis toward the chemokines CXCL12 and CCL21. As well as inducing chemotaxis of tumor cells, ET-1 and ET-2 increased tumor cell invasion through Matrigel. Furthermore, stimulation of macrophage/tumor cell cocultures with ETs led to increased matrix metalloproteinase (MMP)-2 and -9 production by macrophages and a marked increase in invasion of tumor cells. Antagonism of either ET-RA or ET-RB decreased the invasion seen in ET-stimulated cocultures, as did a broad-spectrum MMP inhibitor. Immunohistochemical staining of human breast tumor sections showed increased ET and ET receptor protein expression by tumor cells in invasive ductal carcinoma compared with normal breast tissue or ductal carcinoma in situ. Furthermore, tumor cell ET and receptor expression was stronger at the invasive margin of invasive ductal carcinomas, in the lymphovascular space, and in lymph node metastases. ET expression often colocalized with ET-RB expression in all neoplastic tissue indicating a possible autocrine action of ETs. We suggest that expression of ETs and their receptors by human breast tumors, particularly in conjunction with a high macrophage infiltrate, may have a role in the progression of breast cancer and the invasion of tumor cells.
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PMID:A role for endothelin-2 and its receptors in breast tumor cell invasion. 1505 99

Matrix metalloproteinases (MMPs) are a family of extracellular proteinases whose contributions to cancer progression have been studied because of their matrix-degrading abilities and elevated expression in advanced stage tumors. Recent findings suggest a role for MMPs during the multiple stages of tumor progression including establishment and growth, migration, invasion, metastasis, and angiogenesis. MMP-9 regulation at the molecular level can be studied by measuring the effect(s) of a variety of physiological and pharmacological agents on cells. Multiple signaling molecules such as protein kinase C, pertussis toxin-sensitive guanine nucleotide-binding protein G, and protein tyrosine kinases are known to mediate the secretion of MMPs in cell lines. We previously reported an upregulation of MMP-9 in T cells of mammary tumor-bearing mice. In this study, pharmacologic inhibitors were used to dissect the signaling pathways involved in the upregulation of MMP-9 in the splenic T cells of normal and mammary tumor-bearing mice. Staurosporine, a protein kinase inhibitor, stimulated MMP-9 secretion by normal T lymphocytes, while the constitutively high levels of MMP-9 produced by tumor bearers' T cells were decreased by Genistein, a specific tyrosine kinase inhibitor, and Rottlerin, a PKC inhibitor. Using a NF-kappaB specific probe to the murine MMP-9 promoter, electromobility shift assays of nuclear proteins from normal and tumor bearers' splenic T cells revealed a pattern of higher intensity bands from the tumor bearers' nuclear extracts, indicating a greater amount of these transcription factors bound to the recognition motif. When mammary tumor bearers' T cells were cultured with the NF-kappaB inhibitors, N-p-Tosyl-L-lysine chloromethyl ketone hydrochloride and Bay 11-7082, there was a subsequent decreased production of MMP-9. These results suggest that the tumor burden may be activating various signaling pathways within splenic T lymphocytes to upregulate MMP-9 expression.
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PMID:Molecular events involved in the increased expression of matrix metalloproteinase-9 by T lymphocytes of mammary tumor-bearing mice. 1809 25