Linked Life Data

17203214

Source:http://linkedlifedata.com/resource/pubmed/id/17203214

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-1-4
pubmed:abstractText
Metastatic germ cell tumors (GCT) are curable, however GCTs refractory to cisplatin-based chemotherapy have a poor prognosis. This study explores D-type cyclins as molecular targets in GCTs because all-trans-retinoic acid (RA)-mediated differentiation of the human embryonal carcinoma (EC) cell line NT2/D1 is associated with G1 cell cycle arrest and proteasomal degradation of cyclin D1. RA effects on D-type cyclins are compared in human EC cells that are RA sensitive or dually RA and cisplatin resistant (NT2/D1-R1) and in clinical GCTs that have both EC and mature teratoma components. Notably, GCT differentiation was associated with reduced cyclin D1 but increased cyclin D3 expression. RA was shown here to repress cyclin D1 through a transcriptional mechanism in addition to causing its degradation. The siRNA-mediated repression of individual cyclin D species resulted in growth inhibition in both RA sensitive and resistant EC cells. Only repression of cyclin D1 occurred in vitro and when clinical GCTs mature, implicating cyclin D1 as a molecular therapeutic target. To confirm this, the EGFR-tyrosine kinase inhibitor, Erlotinib, was used to repress cyclin D1. This inhibited proliferation in RA and cisplatin sensitive and resistant EC cells. Taken together, these findings implicate cyclin D1 targeting agents for the treatment of GCTs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
333-40
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Repression of cyclin D1 as a target for germ cell tumors.
pubmed:affiliation
Department of Pharmacology and Toxicology, Dartmouth Medical School, HB 7650, Hanover, NH 03755, USA. sarah.freemantle@dartmouth.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural