Linked Life Data

15273700

Source:http://linkedlifedata.com/resource/pubmed/id/15273700

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2004-10-20
pubmed:abstractText
Endostatin is a cleavage product of collagen XVIII that has shown to inhibit tumor-angiogenesis in experimental tumor models. At present, the exact molecular mechanism of action of endostatin is not completely elucidated. In this study, we wanted to identify specific target genes of endostatin. For this purpose, the human renal cell carcinoma RC-9 was subcutaneously implanted in nude mice and treated with endostatin. Tumor growth was inhibited by endostatin after 4 days of treatment. Using immunohistochemistry and the hypoxia marker pimonidazole, we demonstrate disintegration of blood vessels and hypoxia and anoxia as a result of the treatment. Hereafter, we applied the polymerase chain reaction (PCR)-based subtractive suppression hybridization (SSH) method, together with the mirror orientation selection (MOS) technique to identify specifically induced and suppressed genes after endostatin-treatment. We found eight genes to be specifically induced and 11 to be suppressed by the endostatin-treatment. Among other genes, core binding factor a-1/osteoblast-specific factor-2 (cbfa1/osf2) was found to be specifically suppressed by endostatin. Unexpectedly, cbfa1/osf2 was found to be specifically expressed in granulocytes in the tumor, not only in the experimental RC-9 tumor model, but in sections of human breast cancer as well. Since an effect of antiangiogenic therapy on granulocytes has been reported before, this might lead to new insights in the role of granulocytes in antiangiogenic therapy in general. In conclusion, the SSH-PCR implemented with the MOS-technique is a powerful tool to identify differentially expressed genes. Using these techniques, we have identified several target genes of endostatin, of which cbfa1/osf2 was found to be specifically expressed in granulocytes in the tumor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0023-6837
pubmed:author
pubmed:issnType
Print
pubmed:volume
84
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1472-83
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15273700-Angiogenesis Inhibitors, pubmed-meshheading:15273700-Animals, pubmed-meshheading:15273700-Antineoplastic Agents, pubmed-meshheading:15273700-Breast Neoplasms, pubmed-meshheading:15273700-Carcinoma, Renal Cell, pubmed-meshheading:15273700-Cell Line, Tumor, pubmed-meshheading:15273700-Core Binding Factor Alpha 1 Subunit, pubmed-meshheading:15273700-Core Binding Factors, pubmed-meshheading:15273700-Endostatins, pubmed-meshheading:15273700-Gene Expression Regulation, Neoplastic, pubmed-meshheading:15273700-Granulocytes, pubmed-meshheading:15273700-Humans, pubmed-meshheading:15273700-Kidney Neoplasms, pubmed-meshheading:15273700-Mice, pubmed-meshheading:15273700-Mice, Inbred BALB C, pubmed-meshheading:15273700-Mice, Knockout, pubmed-meshheading:15273700-Mice, Nude, pubmed-meshheading:15273700-Neoplasm Proteins, pubmed-meshheading:15273700-Neoplasm Transplantation, pubmed-meshheading:15273700-Neovascularization, Pathologic, pubmed-meshheading:15273700-Transcription Factors
pubmed:year
2004
pubmed:articleTitle
Identification of differentially expressed genes in a renal cell carcinoma tumor model after endostatin-treatment.
pubmed:affiliation
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't