Linked Life Data

15674848

Source:http://linkedlifedata.com/resource/pubmed/id/15674848

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-2-1
pubmed:abstractText
One of the proposed mechanisms of carcinogenic action of TCDD (=dioxin) on breast cells is that it causes significant inhibition of proper differentiation of mammary duct epithelial cells and thereby increases the number of terminal end buds, which are susceptible to other carcinogens (Fenton et al., Toxicol Sci 2002;67:63-74; Brown et al., Carcinogenesis 1998; 19:1623-1629; Lamartiniere, J Mammary Gland Biol Neoplasia 2002;7:67-76). To address this topic, we selected MCF10A, a line of immortalized normal human breast epithelial cells as an in vitro model. An initial effort was made to optimize the cultural condition of MCF10A cells to promote the cell differentiation effect of insulin. Under this condition, TCDD clearly antagonized the action of insulin only in the presence of cholera toxin that is known to promote the differentiation of normal human breast epithelial cells. To test the hypothesis that TCDD-induced c-Src kinase activation is casually related to this compound's antagonistic action against insulin, we treated MCF10A cells with two c-Src blocking agents, an anti-Src antisense oligonucleotides blocker and a known specific inhibitor of c-Src kinase, PP-2 and studied the effect of insulin and TCDD on cell proliferation. The results showed that, in cells treated with either of these two c-Src blocking agents, the antagonistic effect of TCDD disappeared. It was also found that agents which specifically block the activation of ERK could also abrogate the action of TCDD to suppress insulin signaling. Together, these results indicate that the mechanism of the antagonistic action of TCDD on insulin signaling is mainly mediated through c-Src signaling through activation of ERK.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1095-6670
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
322-31
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
TCDD causes suppression of growth and differentiation of MCF10A, human mammary epithelial cells by interfering with their insulin receptor signaling through c-Src kinase and ERK activation.
pubmed:affiliation
Department of Environmental Toxicology and the Center for Environmental Health Sciences, University of California, Davis, CA 95616, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.