Source:http://linkedlifedata.com/resource/pubmed/id/19997650
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
|
pubmed:dateCreated |
2010-1-12
|
pubmed:abstractText |
Soluble APRIL (sAPRIL), the active form of a proliferation-inducing ligand (APRIL), is implicated in the proliferation of tumor cells. Suppressing APRIL function has been considered as a potential strategy for the therapy of APRIL-associated tumors. In the present study, we generated human sAPRIL and its two mutants, Gln187-D-sAPRIL (Gln187 deleted) and Gly187-sAPRIL (Gln187 replaced by Gly). In vitro experiments showed that the two mutants had similar specific binding capacity to lung carcinoma A549 cells compared to the wild-type sAPRIL, and both, especially Gly187-sAPRIL, exhibited significant antagonistic effect on sAPRIL-induced tumor cell proliferation in a dose-dependent manner, which might be predominantly mediated by blocking sAPRIL-induced MEK and ERK phosphorylation but not p38MAPK or JNK signaling. In vivo experiments with nude mice bearing A549 cell-derived xenograft tumor showed that only the Gly187-sAPRIL mutant could significantly suppress the tumor growth. These results suggest that Gln187 may be a crucial amino acid in APRIL-mediated tumor cell proliferation via the MEK-ERK signaling pathway and that the sAPRIL mutants may serve as novel potential antagonists of APRIL for the therapy of APRIL-associated cancers.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamine,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/TNFSF13 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor Ligand...
|
pubmed:status |
MEDLINE
|
pubmed:issn |
1734-154X
|
pubmed:author | |
pubmed:issnType |
Electronic
|
pubmed:volume |
56
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
703-10
|
pubmed:meshHeading |
pubmed-meshheading:19997650-Amino Acid Sequence,
pubmed-meshheading:19997650-Animals,
pubmed-meshheading:19997650-Cell Line, Tumor,
pubmed-meshheading:19997650-Cell Proliferation,
pubmed-meshheading:19997650-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:19997650-Glutamine,
pubmed-meshheading:19997650-Humans,
pubmed-meshheading:19997650-Lung Neoplasms,
pubmed-meshheading:19997650-MAP Kinase Kinase Kinases,
pubmed-meshheading:19997650-Male,
pubmed-meshheading:19997650-Mice,
pubmed-meshheading:19997650-Sequence Alignment,
pubmed-meshheading:19997650-Signal Transduction,
pubmed-meshheading:19997650-Tumor Necrosis Factor Ligand Superfamily Member 13,
pubmed-meshheading:19997650-Xenograft Model Antitumor Assays
|
pubmed:year |
2009
|
pubmed:articleTitle |
Two Gln187 mutants of human soluble APRIL inhibit proliferation of lung carcinoma A549 cells.
|
pubmed:affiliation |
Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing, China.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|