Linked Life Data

18451150

Source:http://linkedlifedata.com/resource/pubmed/id/18451150

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2008-5-2
pubmed:abstractText
The majority of BRCA1-associated breast cancers are basal cell-like, which is associated with a poor outcome. Using a spontaneous mouse mammary tumor model, we show that platinum compounds, which generate DNA breaks during the repair process, are more effective than doxorubicin in Brca1/p53-mutated tumors. At 0.5 mg/kg of daily cisplatin treatment, 80% primary tumors (n = 8) show complete pathologic response. At greater dosages, 100% show complete response (n = 19). However, after 2 to 3 months of complete remission following platinum treatment, tumors relapse and become refractory to successive rounds of treatment. Approximately 3.8% to 8.0% (mean, 5.9%) of tumor cells express the normal mammary stem cell markers, CD29(hi)24(med), and these cells are tumorigenic, whereas CD29(med)24(-/lo) and CD29(med)24(hi) cells have diminished tumorigenicity or are nontumorigenic, respectively. In partially platinum-responsive primary transplants, 6.6% to 11.0% (mean, 8.8%) tumor cells are CD29(hi)24(med); these populations significantly increase to 16.5% to 29.2% (mean, 22.8%; P < 0.05) in platinum-refractory secondary tumor transplants. Further, refractory tumor cells have greater colony-forming ability than the primary transplant-derived cells in the presence of cisplatin. Expression of a normal stem cell marker, Nanog, is decreased in the CD29(hi)24(med) populations in the secondary transplants. Top2A expression is also down-regulated in secondary drug-resistant tumor populations and, in one case, was accompanied by genomic deletion of Top2A. These studies identify distinct cancer cell populations for therapeutic targeting in breast cancer and implicate clonal evolution and expansion of cancer stem-like cells as a potential cause of chemoresistance.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3243-50
pubmed:dateRevised
2011-1-19
pubmed:meshHeading
pubmed-meshheading:18451150-Animals, pubmed-meshheading:18451150-Antigens, Neoplasm, pubmed-meshheading:18451150-Antineoplastic Agents, pubmed-meshheading:18451150-Cells, Cultured, pubmed-meshheading:18451150-Cisplatin, pubmed-meshheading:18451150-DNA Topoisomerases, Type II, pubmed-meshheading:18451150-DNA-Binding Proteins, pubmed-meshheading:18451150-Disease-Free Survival, pubmed-meshheading:18451150-Dose-Response Relationship, Drug, pubmed-meshheading:18451150-Drug Resistance, Neoplasm, pubmed-meshheading:18451150-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18451150-Genes, BRCA1, pubmed-meshheading:18451150-Genes, p53, pubmed-meshheading:18451150-Mammary Neoplasms, Animal, pubmed-meshheading:18451150-Mice, pubmed-meshheading:18451150-Mice, Inbred C57BL, pubmed-meshheading:18451150-Mice, Knockout, pubmed-meshheading:18451150-Models, Biological, pubmed-meshheading:18451150-Mutation, pubmed-meshheading:18451150-NIH 3T3 Cells, pubmed-meshheading:18451150-Neoplasm Transplantation, pubmed-meshheading:18451150-Neoplastic Stem Cells, pubmed-meshheading:18451150-Tumor Stem Cell Assay
pubmed:year
2008
pubmed:articleTitle
Cancer stem cells contribute to cisplatin resistance in Brca1/p53-mediated mouse mammary tumors.
pubmed:affiliation
Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, CA 92697, USA.
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