Linked Life Data

9368008

Source:http://linkedlifedata.com/resource/pubmed/id/9368008

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
47
pubmed:dateCreated
1997-12-23
pubmed:abstractText
Amplification and overexpression of the HER-2/neu proto-oncogene frequently coincide with an aggressive clinical course of certain human adenocarcinomas. To assess whether HER-2/neu plays a rate-limiting role in ovarian cancer, we used human SK-OV-3 ovarian cancer cells as a model. We applied a conditional mRNA depletion strategy of HER-2/neu with anti-HER-2/neu-targeted hammerhead ribozymes expressed under the control of a tetracycline-regulated promoter system. In these ovarian cancer cells, we reduced HER-2/neu mRNA, protein expression, and tumor growth in nude mice by transfection with HER-2/neu-targeted ribozymes and generated cell lines expressing different levels of HER-2/neu. Expression of the most effective ribozyme (Rz3) quenched HER-2/neu mRNA levels by >90%. Concomitantly, fluorescence-activated cell sorting analysis revealed that expression of the HER-2/neu-encoded surface glycoprotein was almost completely abrogated. In nude mice, tumor growth was dramatically inhibited in the HER-2/neu-depleted Rz3-expressing SK-OV-3 cells. Furthermore, already established tumors started to regress when Rz3 expression was activated midstream by withdrawal of the tetracycline treatment. This study supports the thesis that HER-2/neu can be rate-limiting for the malignant phenotype of ovarian cancer in a gene dose-dependent manner.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
29482-6
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
HER-2/neu is rate-limiting for ovarian cancer growth. Conditional depletion of HER-2/neu by ribozyme targeting.
pubmed:affiliation
Lombardi Cancer Center and Department of Pharmacology, Georgetown University, Washington, D. C. 20007, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't