Linked Life Data

21315112

Source:http://linkedlifedata.com/resource/pubmed/id/21315112

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-4-18
pubmed:abstractText
Insulin-like Growth Factor-1 (IGF-1) plays a key role in breast cancer development and cell cycle regulation. It has been demonstrated that IGF-1 stimulates cyclin expression, thus regulating the G1 to S phase transition of the cell cycle. Potassium (K(+)) channels are involved in the G1 phase progression of the cell cycle induced by growth factors. However, mechanisms that allow growth factors to cooperate with K(+) channels in order to modulate the G1 phase progression and cyclin expression remain unknown. Here, we focused on hEag1 K(+) channels which are over-expressed in breast cancer and are involved in the G1 phase progression of breast cancer cells (MCF-7). As expected, IGF-1 increased cyclin D1 and E expression of MCF-7 cells in a cyclic manner, whereas the increase of CDK4 and 2 levels was sustained. IGF-1 stimulated p21(WAF1/Cip1) expression with a kinetic similar to that of cyclin D1, however p27(Kip1) expression was insensitive to IGF-1. Interestingly, astemizole, a blocker of hEag1 channels, but not E4031, a blocker of HERG channels, inhibited the expression of both cyclins after 6-8h of co-stimulation with IGF-1. However, astemizole failed to modulate CDK4, CDK2, p21(WAF1/Cip1) and p27(Kip1) expression. The down-regulation of hEag1 by siRNA provoked a decrease in cyclin expression. This study is the first to demonstrate that K(+) channels such as hEag1 are directly involved in the IGF-1-induced up-regulation of cyclin D1 and E expression in MCF-7 cells. By identifying more specifically the temporal position of the arrest site induced by the inhibition of hEag1 channels, we confirmed that hEag1 activity is predominantly upstream of the arrest site induced by serum-deprivation, prior to the up-regulation of both cyclins D1 and E. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-3002
pubmed:author
pubmed:copyrightInfo
2011 Elsevier B.V. All rights reserved.
pubmed:issnType
Print
pubmed:volume
1813
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
723-30
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Regulation of IGF-1-dependent cyclin D1 and E expression by hEag1 channels in MCF-7 cells: the critical role of hEag1 channels in G1 phase progression.
pubmed:affiliation
Laboratoire de Physiologie Cellulaire, JE2530, Université de Picardie Jules Verne, 33 Rue St Leu, Amiens, 80039, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't