| 19619627 |
Ptak A, Gut P, Blachuta M, Rak A, Gregoraszczuk EL: 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. Toxicol Lett. 2009 Oct 28;190(2):187-92. Epub 2009 Jul 18.
Our previously published data showed that 260h 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 72h with 4-monochlorobiphenyl (PCB3), 4'-hydroxy-4-monochlorobiphenyl (4-OH-PCB3) or 3'4'-dihydroxy-4-monochlorobiphenyl (3,4-diOH-PCB3) (300nM). 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. |
4(0,0,0,4) |