Source:http://linkedlifedata.com/resource/pubmed/id/16103080
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
16
|
pubmed:dateCreated |
2005-8-16
|
pubmed:abstractText |
Galectin-3 (Gal-3), a pleiotropic carbohydrate-binding protein, is a selective binding partner of activated K-Ras-GTP. Because both proteins are antiapoptotic and associated with cancer progression, we questioned the possible functional role of Gal-3 in K-Ras activation. We found that overexpression of Gal-3 in human breast cancer cells (BT-549/Gal-3) coincided with a significant increase in wild-type (wt) K-Ras-GTP coupled with loss in wt N-Ras-GTP, whereas the nononcogenic Gal-3 mutant proteins [Gal-3(S6E) and Gal-3(G182A)] failed to induce the Ras isoform switch. Only wt Gal-3 protein coimmunoprecipitated and colocalized with oncogenic K-Ras, resulting in its activation with radical alterations in Ras signaling pathway, whereby the activation of AKT and Ral was suppressed and shifted to the activation of extracellular signal-regulated kinase (ERK). Specific inhibitors for Ras or mitogen-activated protein/ERK kinase (farnesylthiosalicylic acid and UO126, respectively) inhibited Gal-3-mediated apoptotic resistance and anchorage-independent growth functions. In conclusion, this study shows that Gal-3 confers on BT-549 human breast carcinoma cells several oncogenic functions by binding to and activation of wt K-Ras, suggesting that some of the molecular functions of Gal-3 are, at least in part, a result of K-Ras activation.
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Aug
|
pubmed:issn |
0008-5472
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
15
|
pubmed:volume |
65
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
7292-300
|
pubmed:dateRevised |
2007-11-14
|
pubmed:meshHeading |
pubmed-meshheading:16103080-Animals,
pubmed-meshheading:16103080-Breast Neoplasms,
pubmed-meshheading:16103080-COS Cells,
pubmed-meshheading:16103080-Cell Line, Tumor,
pubmed-meshheading:16103080-Cercopithecus aethiops,
pubmed-meshheading:16103080-Galectin 3,
pubmed-meshheading:16103080-Humans,
pubmed-meshheading:16103080-MAP Kinase Signaling System,
pubmed-meshheading:16103080-Mutation,
pubmed-meshheading:16103080-Protein Isoforms,
pubmed-meshheading:16103080-ras Proteins
|
pubmed:year |
2005
|
pubmed:articleTitle |
Galectin-3 regulates a molecular switch from N-Ras to K-Ras usage in human breast carcinoma cells.
|
pubmed:affiliation |
Department of Neurobiochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|