Linked Life Data

11751517

Source:http://linkedlifedata.com/resource/pubmed/id/11751517

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2001-12-25
pubmed:abstractText
Previously we have shown that dexamethasone (DEX) enhances the antitumor activity and ligand binding of the active form of vitamin D, 1alpha,25-dihydroxyvitamin D(3) (1,25-D(3)), in the murine squamous cell carcinoma model SCC VII/SF. DEX also reduces the hypercalcemia toxicity of 1,25-D(3) treatment. However, the mechanism of the enhanced antitumor activity has not been defined. Here, we demonstrate that both cell cycle arrest and apoptosis were enhanced by DEX, effects that were inhibited by RU486. We also demonstrate that vitamin D receptor (VDR) protein levels were increased by the combination of 1,25-D(3) and DEX above the level observed with 1,25-D(3) treatment alone, whereas protein levels of the heterodimeric partner of VDR, retinoid X receptor, were lower for the combination than for 1,25-D(3) alone. Glucocorticoid receptor protein levels and ligand binding were increased by 1,25-D(3) but not by the combination. Treatment with the combination of 1,25-D(3) and DEX did not result in greater activation of a vitamin D response element-reporter than 1,25-D(3) alone or of a glucocorticoid response element-reporter than DEX alone. Nevertheless, the levels of phospho-Erk1/2 and phospho-Akt, signaling molecules that are modulated in 1,25-D(3)-treated squamous cell carcinoma cells, were reduced by the combination of 1,25-D(3) and DEX more than by either agent alone. These trends were also observed in vivo. Our results suggest the involvement of the Erk and Akt signaling pathways in the antiproliferative effects of the combination of 1,25-D(3) and DEX and that phospho-Erk1/2 and phospho-Akt may be useful markers of response to this combination.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4164-73
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Combination of 1alpha,25-dihydroxyvitamin D(3) with dexamethasone enhances cell cycle arrest and apoptosis: role of nuclear receptor cross-talk and Erk/Akt signaling.
pubmed:affiliation
Department of Pharmacology, Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't