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PubMed:19087284 JSONTXT

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CoMAGC

Id Subject Object Predicate Lexical cue
T1 1854-1859 Gene denotes Flk-1
E2 1844-1853 Positive_regulation denotes elevating
T2 1906-1919 breast cancer denotes breast cancer
R1 T1 E2 themeOf Flk-1,elevating
R3 T1 T2 CGE-increased Flk-1,breast cancer
R4 T1 T2 CCS-normalTOcancer Flk-1,breast cancer
R5 T1 T2 PT-causality Flk-1,breast cancer
R3 T1 T2 IGE-unidentifiable Flk-1,breast cancer

PubMed_Structured_Abstracts

Id Subject Object Predicate Lexical cue
T1 117-394 BACKGROUND denotes At physiologic concentration in serum, the bile acid sodium deoxycholate (DC) induces survival and migration of breast cancer cells. Here we provide evidence of a novel mechanism by which DC reduces apoptosis that is induced by the sphingolipid ceramide in breast cancer cells.
T2 404-582 METHODS denotes Murine mammacarcinoma 4T1 cells were used in vitro to determine apoptosis and alteration of sphingolipid metabolism by DC, and in vivo to quantify the effect of DC on metastasis.
T3 592-1752 RESULTS denotes We found that DC increased the number of intestinal metastases generated from 4T1 cell tumors grafted into the fat pad. The metastatic nodes contained slowly dividing cancer cells in immediate vicinity of newly formed blood vessels. These cells were positive for CD44, a marker that has been suggested to be expressed on breast cancer stem cells. In culture, a subpopulation (3 +/- 1%) of slowly dividing, CD44+ cells gave rise to rapidly dividing, CD44- cells. DC promoted survival of CD44+ cells, which was concurrent with reduced levels of activated caspase 3 and ceramide, a sphingolipid inducing apoptosis in 4T1 cells. Z-guggulsterone, an antagonist of the farnesoid-X-receptor, obliterated this anti-apoptotic effect, indicating that DC increased cell survival via farnesoid-X-receptor. DC also increased the gene expression of the vascular endothelial growth factor receptor 2 (Flk-1), suggesting that DC enhanced the initial growth of secondary tumors adjacent to blood vessels. The Flk-1 antagonist SU5416 obliterated the reduction of ceramide and apoptosis by DC, indicating that enhanced cell survival is due to Flk-1-induced reduction in ceramide.
T4 1766-2209 CONCLUSIONS denotes Our findings show, for the first time, that DC is a natural tumor promoter by elevating Flk-1 and decreasing ceramide-mediated apoptosis of breast cancer progenitor cells. Reducing the level or effect of serum DC and elevating ceramide in breast cancer progenitor cells by treatment with Z-guggulsterone and/or vascular endothelial growth factor receptor 2/Flk-1 antagonists may thus be a promising strategy to reduce breast cancer metastasis.

PMID_GLOBAL

Id Subject Object Predicate Lexical cue mondo_id
T1 34-47 DiseaseOrPhenotypicFeature denotes breast cancer 0004989|0007254
T3 191-193 DiseaseOrPhenotypicFeature denotes DC 0015780
T4 229-242 DiseaseOrPhenotypicFeature denotes breast cancer 0004989|0007254
T6 305-307 DiseaseOrPhenotypicFeature denotes DC 0015780
T7 374-387 DiseaseOrPhenotypicFeature denotes breast cancer 0004989|0007254
T9 523-525 DiseaseOrPhenotypicFeature denotes DC 0015780
T10 565-567 DiseaseOrPhenotypicFeature denotes DC 0015780
T11 606-608 DiseaseOrPhenotypicFeature denotes DC 0015780
T12 707-710 DiseaseOrPhenotypicFeature denotes pad 0005386
T13 913-926 DiseaseOrPhenotypicFeature denotes breast cancer 0004989|0007254
T15 1010-1014 DiseaseOrPhenotypicFeature denotes gave 0006767
T16 1054-1056 DiseaseOrPhenotypicFeature denotes DC 0015780
T17 1333-1335 DiseaseOrPhenotypicFeature denotes DC 0015780
T18 1386-1388 DiseaseOrPhenotypicFeature denotes DC 0015780
T19 1502-1504 DiseaseOrPhenotypicFeature denotes DC 0015780
T20 1536-1552 DiseaseOrPhenotypicFeature denotes secondary tumors 0024882
T21 1663-1665 DiseaseOrPhenotypicFeature denotes DC 0015780
T22 1810-1812 DiseaseOrPhenotypicFeature denotes DC 0015780
T23 1826-1831 DiseaseOrPhenotypicFeature denotes tumor 0005070
T24 1906-1919 DiseaseOrPhenotypicFeature denotes breast cancer 0004989|0007254
T26 1976-1978 DiseaseOrPhenotypicFeature denotes DC 0015780
T27 2005-2018 DiseaseOrPhenotypicFeature denotes breast cancer 0004989|0007254
T29 2184-2197 DiseaseOrPhenotypicFeature denotes breast cancer 0004989|0007254