Linked Life Data

21356271

Source:http://linkedlifedata.com/resource/pubmed/id/21356271

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2011-5-6
pubmed:abstractText
It is known that estrogen promotes the proliferation of breast cancer cells. Agonists to P2Y(2) receptors promote or suppress proliferation in different cancers. In the present study, the methods of methylthiazoltetrazolium (MTT) assay, real-time RT-PCR, Western blot and fluorescent calcium imaging analysis were used to investigate whether P2Y(2) receptors play a role in the effects of estrogen on the breast cancer cell lines, MCF-7 and MDA-MB-231. We found that P2Y(2) receptors were expressed in both the estrogen receptor alpha (ER(?))-positive breast cancer cell line MCF-7 and the ER(?)-negative breast cancer cell line MDA-MB-231. 17?-Estradiol (17?-E(2)) (1 pM to 1000 nM) promoted proliferation of MCF-7 cells, which was blocked by the ER antagonist ICI 182,780 (1 ?M) and the ER(?) antagonist methyl-piperidino-pyrazole (MPP, 50 ?M), but not by the ER(?) antagonist 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP, 50 ?M) or ER(?) small interfering RNA. The P2Y(2) and P2Y(4) receptor agonist UTP (10-100 ?M) suppressed the viability of breast cancer cells in both MCF-7 and MDA-MB-231 cells. The effect was blocked by suramin (10-100 ?M), known to be an effective antagonist against P2Y(2), but not P2Y(4), receptor-mediated responses. 17?-E(2) played a more positive role in promoting proliferation in MCF-7 cells when suramin blocked the functional P2Y(2) receptors. 17?-E(2) (0.1-1000 nM) downregulated the expression of P2Y(2) receptors in terms of both mRNA and protein levels in MCF-7 cells. The effect was blocked by ICI 182,780 and MPP, but not PHTPP or ER(?) small interfering RNA. 17?-E(2) did not affect the expression of P2Y(2) receptors in MDA-MB-231. UTP (10-100 ?M) led to a sharp increase in intracellular Ca(2+) in MCF-7 cells. Pre-incubation with 17?-E(2) (0.1 ?M) attenuated UTP-induced [Ca(2+)](i), which was blocked by ICI182,780 and MPP, but not PHTPP. It is suggested that estrogen, via ER(?) receptors, promotes proliferation of breast cancer cells by down-regulating P2Y(2) receptor expression and attenuating P2Y(2)-induced increase of [Ca(2+)](i).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1872-8057
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
338
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28-37
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
P2Y2 receptor-mediated modulation of estrogen-induced proliferation of breast cancer cells.
pubmed:affiliation
Department of Physiology and The Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai, PR China. elisadayli@yahoo.com.cn
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't