Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
15
|
| pubmed:dateCreated |
1998-8-27
|
| pubmed:abstractText |
The epidermal growth factor-like receptor tyrosine kinase (ErbB) family is frequently overexpressed in a variety of human carcinomas, including breast cancer. To assist in characterizing the role of ErbB-4 in breast cancer, we generated three specific hammerhead ribozymes targeted to the ErbB-4 mRNA. These ribozymes, Rz6, Rz21, and Rz29, efficiently catalyzed the specific cleavage of ErbB-4 message in a cell-free system. We demonstrated that the neuregulin-induced mitogenic effect was abolished in ribozyme Rz29- and Rz6-transfected 32D/ErbB-4 cells. Inhibition of mitogenesis was characterized by ribozyme-mediated down-regulation of ErbB-4 expression. In addition, we provide the first evidence that different threshold levels of ErbB-4 expression and activation correlate with different responses to neuregulin stimulation. High levels of ErbB-4 expression, phosphorylation, and homodimerization are necessary for neuregulin-stimulated, interleukin 3-independent cell proliferation in the 32D/E4 cells. In the case of Rz29-transfected 32D/E4 cells, low levels of ErbB-4 expression allowed neuregulin-induced phosphorylation but were insufficient to couple the activated receptor to cellular signaling. Furthermore, expression of the functional ErbB-4 ribozyme in T47D human breast carcinoma cells led to a down-regulation of endogenous ErbB-4 expression and a reduction of anchorage-independent colony formation. These studies support the use of ErbB-4 ribozymes to define the role of ErbB-4 receptors in human cancers.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-3,
http://linkedlifedata.com/resource/pubmed/chemical/Neuregulins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Catalytic,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/receptor tyrosine-protein kinase...
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
0008-5472
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
58
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3415-22
|
| pubmed:dateRevised |
2011-11-2
|
| pubmed:meshHeading |
pubmed-meshheading:9699674-Animals,
pubmed-meshheading:9699674-Breast Neoplasms,
pubmed-meshheading:9699674-Cell Division,
pubmed-meshheading:9699674-Cell-Free System,
pubmed-meshheading:9699674-Cells, Cultured,
pubmed-meshheading:9699674-DNA,
pubmed-meshheading:9699674-Down-Regulation,
pubmed-meshheading:9699674-Glycoproteins,
pubmed-meshheading:9699674-Hematopoietic System,
pubmed-meshheading:9699674-Humans,
pubmed-meshheading:9699674-Interleukin-3,
pubmed-meshheading:9699674-Mice,
pubmed-meshheading:9699674-Neuregulins,
pubmed-meshheading:9699674-Phosphorylation,
pubmed-meshheading:9699674-RNA, Catalytic,
pubmed-meshheading:9699674-RNA, Messenger,
pubmed-meshheading:9699674-Receptor, Epidermal Growth Factor,
pubmed-meshheading:9699674-Stimulation, Chemical,
pubmed-meshheading:9699674-Substrate Specificity
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
ErbB-4 ribozymes abolish neuregulin-induced mitogenesis.
|
| pubmed:affiliation |
Department of Biochemistry, Georgetown University Medical Center, Washington, DC 20007-2197, USA. Tangc@gunet.georgetown.edu
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
|