Linked Life Data

16619240

Source:http://linkedlifedata.com/resource/pubmed/id/16619240

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-5-31
pubmed:abstractText
Insulin-like growth factor-I receptor (IGF-IR) is often overexpressed in malignant tumors, and is involved in the establishment and maintenance of malignant phenotypes. Tyrosine kinase receptor endocytosis is commonly triggered by ligand binding and occurs via clathrin-coated vescicles that transfer the receptor to the lysosome system for degradation. Our study aims at the evaluation of the mechanisms involved in IGF-IR downregulation in neoplastic (Npl) and non-neoplastic (non-Npl) cells. Exposure to insulin-like growth factor-I (IGF-I) of human lung adenocarcinoma cell lines (A549 and H1299) triggers IGF-IR ubiquitination and internalization processes that require energy and are preceded by the phosphorylation of receptor tyrosines. Differently from other plasma membrane substrates of the ubiquitin system, IGF-IR is degraded mostly by the proteasome in these tumor cell lines. The degradation is inhibited by lactacystin and unaffected by lysosomal inhibitors such as bafilomycin A1 and NH(4)Cl. IGF-IR is processed in a similar manner also in fresh specimens of human lung tumors, while it requires active lysosomal functions in non-Npl human lung tissues. These results suggest that the degradation routes of ubiquitinated IGF-IR diverge in normal and Npl cells, and further support the involvement of IGF-IR signaling in cancer. Such a different route for IGF-IR processing might take place sometime during development, since both proteasome and lysosome pathways are active in fetal lung human fibroblasts, IMR90 cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9541
pubmed:author
pubmed:issnType
Print
pubmed:volume
208
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
354-62
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Degradation of insulin-like growth factor-I receptor occurs via ubiquitin-proteasome pathway in human lung cancer cells.
pubmed:affiliation
Laboratory of Pharmacology, Department of Medicine, Surgery, and Dentistry, University of Milan, Milan, Italy.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't