کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2196610 | 1550932 | 2011 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: P2Y2 receptor-mediated modulation of estrogen-induced proliferation of breast cancer cells P2Y2 receptor-mediated modulation of estrogen-induced proliferation of breast cancer cells](/preview/png/2196610.png)
It is known that estrogen promotes the proliferation of breast cancer cells. Agonists to P2Y2 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 P2Y2 receptors play a role in the effects of estrogen on the breast cancer cell lines, MCF-7 and MDA-MB-231. We found that P2Y2 receptors were expressed in both the estrogen receptor alpha (ERα)-positive breast cancer cell line MCF-7 and the ERα-negative breast cancer cell line MDA-MB-231. 17β-Estradiol (17β-E2) (1 pM to 1000 nM) promoted proliferation of MCF-7 cells, which was blocked by the ER antagonist ICI 182,780 (1 μM) and the ERα antagonist methyl-piperidino-pyrazole (MPP, 50 μM), but not by the ERβ antagonist 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP, 50 μM) or ERβ small interfering RNA. The P2Y2 and P2Y4 receptor agonist UTP (10–100 μM) suppressed the viability of breast cancer cells in both MCF-7 and MDA-MB-231 cells. The effect was blocked by suramin (10–100 μM), known to be an effective antagonist against P2Y2, but not P2Y4, receptor-mediated responses. 17β-E2 played a more positive role in promoting proliferation in MCF-7 cells when suramin blocked the functional P2Y2 receptors. 17β-E2 (0.1–1000 nM) downregulated the expression of P2Y2 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 ERβ small interfering RNA. 17β-E2 did not affect the expression of P2Y2 receptors in MDA-MB-231. UTP (10–100 μM) led to a sharp increase in intracellular Ca2+ in MCF-7 cells. Pre-incubation with 17β-E2 (0.1 μM) attenuated UTP-induced [Ca2+]i, which was blocked by ICI182,780 and MPP, but not PHTPP. It is suggested that estrogen, via ERα receptors, promotes proliferation of breast cancer cells by down-regulating P2Y2 receptor expression and attenuating P2Y2-induced increase of [Ca2+]i.
Journal: Molecular and Cellular Endocrinology - Volume 338, Issues 1–2, 16 May 2011, Pages 28–37