Linked Life Data

18575751

Source:http://linkedlifedata.com/resource/pubmed/id/18575751

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-6-25
pubmed:abstractText
CCN1 plays diverse roles in cellular proliferation, survival, migration and angiogenesis. We determined the relationship between CCN1 protein expression and clinical factors that are important for the classification of breast cancer. CCN1 contains four functional domains; the contribution of each of the structural domains to the biological properties of CCN1 in breast cancer was investigated. We performed immunohistochemistry for CCN1 on a breast cancer tissue array, and conducted a detailed statistical analysis on the relationship between CCN1 protein expression and clinical factors that are important for the classification of breast cancer. The structure-function relationship was examined using four mutant constructs in which one of the modules (DM1-DM4) had been deleted. MCF-7 breast cancer cells were stably transfected with these constructs and their biological activity was tested in comparison to full-length CCN1. Staining of CCN1 in tumors was positively correlated with AJCC disease stage. A strong association also was found between lymph node involvement and high CCN1 expression in patients with invasive breast cancer; there was a significant increase in the breast cancer expression of CCN1 in patients with positive lymph nodes (P=0.004), and the levels of CCN1 correlated with the number of positive lymph nodes (P=0.0006). Deletion of module 4 rendered CCN1 unable to either bind heparin or associate with the extracellular matrix. Furthermore, MCF-7/DM4 cells demonstrated reduced cell spreading, migration and proliferation, indicating that module 4 of the protein is important for its ability to promote these activities. These findings indicate that CCN1 is involved throughout the clinical progression of breast cancer to an invasive phenotype. The multimodular structure of CCN1 enables it to fulfill multiple functions that may contribute to the different stages of cancer development, raising the prospect that specific regions of CCN1 could be targeted for therapeutic benefit to inhibit particular aspects of malignancy in breast cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
59-67
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Functional domains of CCN1 (Cyr61) regulate breast cancer progression.
pubmed:affiliation
Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA. james.okelly@gmail.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural