Linked Life Data

17638897

Source:http://linkedlifedata.com/resource/pubmed/id/17638897

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2007-7-19
pubmed:abstractText
Women are at higher risk for the development of lung adenocarcinoma than men; however, the mechanisms responsible for this are poorly understood. In lung adenocarcinoma cells, the estrogen receptor beta (ERbeta) is the predominating form. We found that 17beta-estradiol enhanced proliferation of the putative cells of origin of lung adenocarcinoma, small airway epithelial cells (HPLD1), in response to the nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Reverse-phase protein microarrays combined with Western blotting revealed that NNK induced phosphorylation of ERbeta, an effect that involved stimulation of the adrenergic receptors beta1 (beta1AR). In transiently transfected cells, beta1AR coprecipitated with ERbeta, which increased with NNK treatment. ERbeta enhanced NNK-induced cyclic AMP accumulation as well as Galphai-mediated mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) 1/2 activation. Coexpression of beta1AR and ERbeta activated NNK-mediated ERK1/2 cooperatively. ERbeta gene knockdown, as well as coexpression of the dominant negative Ras and Raf, reduced stimulation of ERK1/2 by NNK. Whereas NNK phosphorylated Akt at Thr(308) and Ser(473), ERbeta had no effect on this activity. Luciferase reporter assays showed that, in response to NNK, ERbeta stimulated transcription of serum responsive element (SRE) but had a very small effect on the activity of estrogen responsive element (ERE). Together, the phosphorylation of ERbeta, the dependence on Galphai proteins, the activation of ERK1/2, and the preferential targeting of SRE over the classic ERE pathway support a role for nongenomic ERbeta in the development of smoking-associated lung cancer. This novel cooperation between beta1AR and ERbeta signaling may contribute to the prominence of lung adenocarcinoma in women.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6863-71
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Nongenomic beta estrogen receptors enhance beta1 adrenergic signaling induced by the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in human small airway epithelial cells.
pubmed:affiliation
Experimental Oncology Laboratory, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural