Linked Life Data

16166314

Source:http://linkedlifedata.com/resource/pubmed/id/16166314

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2005-9-16
pubmed:abstractText
Tumor metastasis is the major cause of morbidity and mortality in patients with breast cancer. It is critical to identify metastasis enabling genes and understand how they are responsible for inducing specific aspects of the metastatic phenotype to allow for improved clinical detection and management. Protein kinase C epsilon (PKC epsilon), a member of a family of serine/threonine protein kinases, is a transforming oncogene that has been reported to be involved in cell invasion and motility. In this study, we investigated the role of PKC epsilon in breast cancer development and progression. High-density tissue microarray analysis showed that PKC epsilon protein was detected in 73.6% (106 of 144) of primary tumors from invasive ductal breast cancer patients. Increasing PKC epsilon staining intensity was associated with high histologic grade (P = 0.0206), positive Her2/neu receptor status (P = 0.0419), and negative estrogen (P = 0.0026) and progesterone receptor status (P = 0.0008). Kaplan-Meier analyses showed that PKC epsilon was significantly associated with poorer disease-free and overall survival (log-rank, P = 0.0478 and P = 0.0414, respectively). RNA interference of PKC epsilon in MDA-MB231 cells, an aggressive breast cancer cell line with elevated PKC epsilon levels, resulted in a cell phenotype that was significantly less proliferative, invasive, and motile than the parental or the control RNA interference transfectants. Moreover, in vivo tumor growth of small interfering RNA-PKC epsilon MDA-MB231 clones was retarded by a striking 87% (P < 0.05) and incidence of lung metastases was inhibited by 83% (P < 0.02). PKC epsilon-deficient clones were found to have lower RhoC GTPase protein levels and activation. Taken together, these results revealed that PKC epsilon plays a critical and causative role in promoting an aggressive metastatic breast cancer phenotype and as a target for anticancer therapy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8366-71
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16166314-Animals, pubmed-meshheading:16166314-Breast Neoplasms, pubmed-meshheading:16166314-Carcinoma, Ductal, Breast, pubmed-meshheading:16166314-Cell Growth Processes, pubmed-meshheading:16166314-Cell Line, Tumor, pubmed-meshheading:16166314-Disease-Free Survival, pubmed-meshheading:16166314-Female, pubmed-meshheading:16166314-Humans, pubmed-meshheading:16166314-Mice, pubmed-meshheading:16166314-Mice, Nude, pubmed-meshheading:16166314-Predictive Value of Tests, pubmed-meshheading:16166314-Protein Kinase C-epsilon, pubmed-meshheading:16166314-RNA, Small Interfering, pubmed-meshheading:16166314-RNA Interference, pubmed-meshheading:16166314-Tumor Markers, Biological, pubmed-meshheading:16166314-Xenograft Model Antitumor Assays, pubmed-meshheading:16166314-ras Proteins, pubmed-meshheading:16166314-rho GTP-Binding Proteins
pubmed:year
2005
pubmed:articleTitle
Protein kinase C epsilon is a predictive biomarker of aggressive breast cancer and a validated target for RNA interference anticancer therapy.
pubmed:affiliation
Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan Health System, Ann Arbor, Michigan 48109, USA. qpan@med.umich.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural