Linked Life Data

17492783

Source:http://linkedlifedata.com/resource/pubmed/id/17492783

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-7-26
pubmed:abstractText
The identification of molecular determinants involved in the promotion of metastasis and development of androgen insensitive prostate cancer (AI-PCa) is necessary to discriminate aggressive from indolent disease and to identify therapeutic targets for advanced disease. Overexpression of one particular member of the insulin like growth factor (IGF) axis, IGFBP-2, is implicated in the development of AI-PCa and other cancers. Using the LNCaP human PCa progression model, we show that the AI and metastatic prostate cancer cell line C4-2B4 expresses greater amounts of secreted IGFBP-2 than the androgen sensitive (AS), non-metastatic LNCaP progenitor cell line. Further, the ability of androgens to decrease extracellular IGFBP-2 levels is attenuated in the AI and metastatic C4-2 cell line. The ability of androgen to negatively regulate extracellular IGFBP-2 levels was blocked by Casodex in a dose-dependent manner. The mechanism underlying the androgen-induced downregulation of secreted IGFBP-2 appears to involve extracellular proteolysis, resulting in the production of IGFBP-2 fragments lacking the ability to bind IGF-I and IGF-II. As C4-2 cells have an attenuated ability to proteolyze IGFBP-2 in response to androgen and C4-2B4 cells express greater amounts of IGFBP-2, our data implies that the diminished regulation of IGFBP-2 and loss of associated proteolytic fragments play a role in the increased metastatic behavior of these cells in vivo. Furthermore, our results suggest that either increased levels of intact IGFBP-2 or decreased levels of IGFBP-2 proteolytic fragments could serve as a biomarker to monitor for progression to AI-PCa.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9541
pubmed:author
pubmed:copyrightInfo
(c) 2007 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
213
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
261-8
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Hormonal regulation of IGFBP-2 proteolysis is attenuated with progression to androgen insensitivity in the LNCaP progression model.
pubmed:affiliation
Laboratory for Cancer Ontogeny and Therapeutics, Department of Biological Sciences, University of Delaware, Newark, Deleware 19716, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural