Linked Life Data

18470911

Source:http://linkedlifedata.com/resource/pubmed/id/18470911

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-6-3
pubmed:abstractText
Breast cancer metastasis suppressor 1 (BRMS1) inhibits the ability of multiple human and murine cancer cell lines to metastasize to lymph nodes, bones and lungs. Comparison of mRNA expression in metastatic MDA-MB-435 human carcinoma cells (435) and metastasis-suppressed BRMS1 transfectants (435/BRMS1) showed a marked (>90%) reduction of osteopontin (OPN) mRNA and protein expression in BRMS1-overexpressing cells. OPN expression is associated with disease progression in patients, with higher levels of OPN produced by cancer cells associated with poorer patient survival. Furthermore, OPN has been suggested to promote survival of cancer cells in response to stress, although the mechanisms by which this may occur remain poorly understood. This study tested the hypothesis that re-expression of OPN in metastasis-suppressed 435/BRMS1 cells would reverse metastasis suppression and confer protection from stress-induced apoptosis. A stable pooled population of OPN overexpressing 435/BRMS1 cells was created (435/BRMS1/OPN). OPN re-expression did not affect in vitro cell growth rates; however, increased anchorage independent growth/survival and protection from hypoxia-induced apoptosis was observed (p < 0.05). In vivo, OPN re-expression in BRMS1 transfected cells did not affect in vivo primary tumor growth but did increase the incidence of spontaneous metastasis to lymph nodes and lungs in mice. These novel findings suggest that OPN downregulation by BRMS1 may be responsible, at least in part, for BRMS1-mediated metastasis suppression by sensitizing cancer cells to stress induced apoptosis. These studies clarify one mechanism by which BRMS1 can suppress metastasis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1097-0215
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
123
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
526-34
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Downregulation of osteopontin contributes to metastasis suppression by breast cancer metastasis suppressor 1.
pubmed:affiliation
London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural