PubMed:16682955 JSON TXT

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DisGeNET5_gene_disease

DisGeNet-2017-sample

{"project":"DisGeNet-2017-sample","denotations":[{"id":"T437","span":{"begin":2109,"end":2114},"obj":"gene:10818"},{"id":"T438","span":{"begin":2183,"end":2197},"obj":"disease:C0006142"},{"id":"T2547","span":{"begin":274,"end":291},"obj":"gene:2099"},{"id":"T2548","span":{"begin":343,"end":356},"obj":"disease:C0006142"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T437","obj":"T438"},{"id":"R2","pred":"associated_with","subj":"T437","obj":"T438"},{"id":"R1","pred":"associated_with","subj":"T2547","obj":"T2548"},{"id":"R2","pred":"associated_with","subj":"T2547","obj":"T2548"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"Expression of the SNT-1/FRS2 phosphotyrosine binding domain inhibits activation of MAP kinase and PI3-kinase pathways and antiestrogen resistant growth induced by FGF-1 in human breast carcinoma cells.\nFibroblast growth factor (FGF) signaling can bypass the requirement for estrogen receptor (ER) activation in the growth of ER-positive (ER+) breast cancer cells. Fibroblast growth factor-1 stimulation leads to phosphorylation of the adaptor protein Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target (SNT-1) on C-terminal tyrosine residues, whereas it is constitutively bound through its N-terminal phosphotyrosine-binding domain (PTB) to FGF receptors (FGFRs). By expressing the PTB domain of SNT-1 (SNT-1 PTB) in an inducible manner in an ER+ breast carcinoma line, ML20, we asked whether we could uncouple FGFR activation from its downstream signaling components and abrogate FGF-1-induced antiestrogen-resistant growth. Induction of SNT-1 PTB resulted in a significant decrease of FGF-1-dependent tyrosine phosphorylation of endogenous SNT-1, strong inhibition of complex formation between SNT-1, Gab-1 and Sos-1, and reduced activation of Ras, mitogen-activated protein kinase (MAP kinase), and Akt. SNT-1 PTB also inhibited the phosphorylation of p70S6K on Thr421/Ser424 and Ser411, which may result from the abrogation of MAP kinase activity. Moreover, we also observed a decreased phosphorylation of the MAP kinase-independent site Thr389. This may reflect both inhibition of PI-3 kinase pathways and mammalian target of rapamycin (mTOR)-dependent signaling, as the phosphorylation of Thr389 site was sensitive to treatment with the PI3-K and mTOR inhibitors, LY294002 and rapamycin, respectively. Collectively these results suggest that SNT-1 plays a pivotal role in FGF-dependent activation of the Ras-MAP kinase, PI-3 kinase, and mTOR pathways in these cells. Fibroblast growth factor-1 dependent colony formation of ML20 cells in media containing the pure antiestrogen ICI 182,780 was also markedly inhibited upon induction of SNT-1 PTB, suggesting that blockade of FGFR-SNT-1 interactions might abrogate FGF-mediated antiestrogen resistance in breast cancers."}

sentences

{"project":"sentences","denotations":[{"id":"TextSentencer_T1","span":{"begin":0,"end":201},"obj":"Sentence"},{"id":"TextSentencer_T2","span":{"begin":202,"end":363},"obj":"Sentence"},{"id":"TextSentencer_T3","span":{"begin":364,"end":687},"obj":"Sentence"},{"id":"TextSentencer_T4","span":{"begin":688,"end":949},"obj":"Sentence"},{"id":"TextSentencer_T5","span":{"begin":950,"end":1230},"obj":"Sentence"},{"id":"TextSentencer_T6","span":{"begin":1231,"end":1375},"obj":"Sentence"},{"id":"TextSentencer_T7","span":{"begin":1376,"end":1473},"obj":"Sentence"},{"id":"TextSentencer_T8","span":{"begin":1474,"end":1731},"obj":"Sentence"},{"id":"TextSentencer_T9","span":{"begin":1732,"end":1896},"obj":"Sentence"},{"id":"TextSentencer_T10","span":{"begin":1897,"end":2198},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":201},"obj":"Sentence"},{"id":"T2","span":{"begin":202,"end":363},"obj":"Sentence"},{"id":"T3","span":{"begin":364,"end":687},"obj":"Sentence"},{"id":"T4","span":{"begin":688,"end":949},"obj":"Sentence"},{"id":"T5","span":{"begin":950,"end":1230},"obj":"Sentence"},{"id":"T6","span":{"begin":1231,"end":1375},"obj":"Sentence"},{"id":"T7","span":{"begin":1376,"end":1473},"obj":"Sentence"},{"id":"T8","span":{"begin":1474,"end":1731},"obj":"Sentence"},{"id":"T9","span":{"begin":1732,"end":1896},"obj":"Sentence"},{"id":"T10","span":{"begin":1897,"end":2198},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Expression of the SNT-1/FRS2 phosphotyrosine binding domain inhibits activation of MAP kinase and PI3-kinase pathways and antiestrogen resistant growth induced by FGF-1 in human breast carcinoma cells.\nFibroblast growth factor (FGF) signaling can bypass the requirement for estrogen receptor (ER) activation in the growth of ER-positive (ER+) breast cancer cells. Fibroblast growth factor-1 stimulation leads to phosphorylation of the adaptor protein Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target (SNT-1) on C-terminal tyrosine residues, whereas it is constitutively bound through its N-terminal phosphotyrosine-binding domain (PTB) to FGF receptors (FGFRs). By expressing the PTB domain of SNT-1 (SNT-1 PTB) in an inducible manner in an ER+ breast carcinoma line, ML20, we asked whether we could uncouple FGFR activation from its downstream signaling components and abrogate FGF-1-induced antiestrogen-resistant growth. Induction of SNT-1 PTB resulted in a significant decrease of FGF-1-dependent tyrosine phosphorylation of endogenous SNT-1, strong inhibition of complex formation between SNT-1, Gab-1 and Sos-1, and reduced activation of Ras, mitogen-activated protein kinase (MAP kinase), and Akt. SNT-1 PTB also inhibited the phosphorylation of p70S6K on Thr421/Ser424 and Ser411, which may result from the abrogation of MAP kinase activity. Moreover, we also observed a decreased phosphorylation of the MAP kinase-independent site Thr389. This may reflect both inhibition of PI-3 kinase pathways and mammalian target of rapamycin (mTOR)-dependent signaling, as the phosphorylation of Thr389 site was sensitive to treatment with the PI3-K and mTOR inhibitors, LY294002 and rapamycin, respectively. Collectively these results suggest that SNT-1 plays a pivotal role in FGF-dependent activation of the Ras-MAP kinase, PI-3 kinase, and mTOR pathways in these cells. Fibroblast growth factor-1 dependent colony formation of ML20 cells in media containing the pure antiestrogen ICI 182,780 was also markedly inhibited upon induction of SNT-1 PTB, suggesting that blockade of FGFR-SNT-1 interactions might abrogate FGF-mediated antiestrogen resistance in breast cancers."}

UBERON-AE

{"project":"UBERON-AE","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":178,"end":184},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":343,"end":349},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"},{"id":"PD-UBERON-AE-B_T3","span":{"begin":771,"end":777},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"},{"id":"PD-UBERON-AE-B_T4","span":{"begin":2183,"end":2189},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"}],"text":"Expression of the SNT-1/FRS2 phosphotyrosine binding domain inhibits activation of MAP kinase and PI3-kinase pathways and antiestrogen resistant growth induced by FGF-1 in human breast carcinoma cells.\nFibroblast growth factor (FGF) signaling can bypass the requirement for estrogen receptor (ER) activation in the growth of ER-positive (ER+) breast cancer cells. Fibroblast growth factor-1 stimulation leads to phosphorylation of the adaptor protein Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target (SNT-1) on C-terminal tyrosine residues, whereas it is constitutively bound through its N-terminal phosphotyrosine-binding domain (PTB) to FGF receptors (FGFRs). By expressing the PTB domain of SNT-1 (SNT-1 PTB) in an inducible manner in an ER+ breast carcinoma line, ML20, we asked whether we could uncouple FGFR activation from its downstream signaling components and abrogate FGF-1-induced antiestrogen-resistant growth. Induction of SNT-1 PTB resulted in a significant decrease of FGF-1-dependent tyrosine phosphorylation of endogenous SNT-1, strong inhibition of complex formation between SNT-1, Gab-1 and Sos-1, and reduced activation of Ras, mitogen-activated protein kinase (MAP kinase), and Akt. SNT-1 PTB also inhibited the phosphorylation of p70S6K on Thr421/Ser424 and Ser411, which may result from the abrogation of MAP kinase activity. Moreover, we also observed a decreased phosphorylation of the MAP kinase-independent site Thr389. This may reflect both inhibition of PI-3 kinase pathways and mammalian target of rapamycin (mTOR)-dependent signaling, as the phosphorylation of Thr389 site was sensitive to treatment with the PI3-K and mTOR inhibitors, LY294002 and rapamycin, respectively. Collectively these results suggest that SNT-1 plays a pivotal role in FGF-dependent activation of the Ras-MAP kinase, PI-3 kinase, and mTOR pathways in these cells. Fibroblast growth factor-1 dependent colony formation of ML20 cells in media containing the pure antiestrogen ICI 182,780 was also markedly inhibited upon induction of SNT-1 PTB, suggesting that blockade of FGFR-SNT-1 interactions might abrogate FGF-mediated antiestrogen resistance in breast cancers."}

performance-test

{"project":"performance-test","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":178,"end":184},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":343,"end":349},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"},{"id":"PD-UBERON-AE-B_T3","span":{"begin":771,"end":777},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"},{"id":"PD-UBERON-AE-B_T4","span":{"begin":2183,"end":2189},"obj":"http://purl.obolibrary.org/obo/UBERON_0000310"}],"text":"Expression of the SNT-1/FRS2 phosphotyrosine binding domain inhibits activation of MAP kinase and PI3-kinase pathways and antiestrogen resistant growth induced by FGF-1 in human breast carcinoma cells.\nFibroblast growth factor (FGF) signaling can bypass the requirement for estrogen receptor (ER) activation in the growth of ER-positive (ER+) breast cancer cells. Fibroblast growth factor-1 stimulation leads to phosphorylation of the adaptor protein Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target (SNT-1) on C-terminal tyrosine residues, whereas it is constitutively bound through its N-terminal phosphotyrosine-binding domain (PTB) to FGF receptors (FGFRs). By expressing the PTB domain of SNT-1 (SNT-1 PTB) in an inducible manner in an ER+ breast carcinoma line, ML20, we asked whether we could uncouple FGFR activation from its downstream signaling components and abrogate FGF-1-induced antiestrogen-resistant growth. Induction of SNT-1 PTB resulted in a significant decrease of FGF-1-dependent tyrosine phosphorylation of endogenous SNT-1, strong inhibition of complex formation between SNT-1, Gab-1 and Sos-1, and reduced activation of Ras, mitogen-activated protein kinase (MAP kinase), and Akt. SNT-1 PTB also inhibited the phosphorylation of p70S6K on Thr421/Ser424 and Ser411, which may result from the abrogation of MAP kinase activity. Moreover, we also observed a decreased phosphorylation of the MAP kinase-independent site Thr389. This may reflect both inhibition of PI-3 kinase pathways and mammalian target of rapamycin (mTOR)-dependent signaling, as the phosphorylation of Thr389 site was sensitive to treatment with the PI3-K and mTOR inhibitors, LY294002 and rapamycin, respectively. Collectively these results suggest that SNT-1 plays a pivotal role in FGF-dependent activation of the Ras-MAP kinase, PI-3 kinase, and mTOR pathways in these cells. Fibroblast growth factor-1 dependent colony formation of ML20 cells in media containing the pure antiestrogen ICI 182,780 was also markedly inhibited upon induction of SNT-1 PTB, suggesting that blockade of FGFR-SNT-1 interactions might abrogate FGF-mediated antiestrogen resistance in breast cancers."}

DisGeNET