کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2601019 1133294 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Direct inhibition of ERK1/2 phosphorylation as a possible mechanism for the antiproliferative action of 3,4-diOH-PCB3 in the MCF-7 cell line
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Direct inhibition of ERK1/2 phosphorylation as a possible mechanism for the antiproliferative action of 3,4-diOH-PCB3 in the MCF-7 cell line
چکیده انگلیسی

Our previously published data showed that 260 h of exposure to 3,4-diOH-PCB3 decreased proliferation in the MCF-7 cell line. In the present study, we sought to determine whether this is due to action on the SHBG/cAMP/PKA system, activation of which can inhibit cell proliferation, or to direct inhibition of ERK1/2 phosphorylation. MCF-7 human breast cancer cells were treated for 72 h with 4-monochlorobiphenyl (PCB3), 4′-hydroxy-4-monochlorobiphenyl (4-OH-PCB3) or 3′4′-dihydroxy-4-monochlorobiphenyl (3,4-diOH-PCB3) (300 nM). After the completion of the treatment, cell proliferation was measured with a BrdU incorporation assay. SHBG, cAMP, PKA and ERK1/2 levels in the cells were determined via ELISA.PCB3 and 4-OH-PCB3 had no effect on extra- or intracellular SHBG levels, while a stimulation of SHBG intra- but not extracellular levels was noted in cells exposed to 3,4-diOH-PCB3. Both, pre- and co-incubation with SHBG decreased the proliferation of 3,4-diOH-PCB3-treated cells. Neither PCB3 nor its metabolite had an effect on the cAMP/PKA pathway. A decrease of both ERK1/2 forms was noted under the influence of 3,4-diOH-PCB3. In conclusion, the data presented clearly showed that the antiproliferative action of 3,4-diOH-PCB3 is not mediated by activation of the SHBG/AMP/PKA pathway, but many other plasma membrane receptors seem to be involved in the non-genomic action of 3,4-diOH-PCB3, and instead is due to direct inhibition of the ERK1/2 system.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 190, Issue 2, 28 October 2009, Pages 187–192
نویسندگان
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