Investigating the effect of visfatin on ERalpha phosphorylation (Ser118 and Ser167) and ERE-dependent transcriptional activity
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Date
2018-06-04
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Abstract
Obesity is associated with higher postmenopausal breast cancer incidence. Visfatin level alteration is one of the
mechanisms by which obesity promotes cancer. Ligand-independent activation of estrogen receptor alpha (ERα)
is also associated with carcinogenesis. The activity of ERα is modulated through phosphorylation on multiple sites
by a number of protein kinases. Here we investigated the effect of visfatin as a novel adipocytokine on the phosphorylation
and activity of ERα in MCF-7 breast cancer cells. We showed that exogenous administration of visfatin
significantly increased the phosphorylation of ERα at serine 118 (Ser118) and 167 (Ser167) residues. Visfatininduced
Ser118 phosphorylation was diminished after treatment of cells with U0126 (MEK1/2 inhibitor). Furthermore,
our results showed that visfatin-induced Ser167 phosphorylation is mediated through both MAPK and
PI3K/Akt signaling pathways. Inhibition of the enzymatic activity of visfatin by FK866 had no effect on phosphorylation
of ERα. We also showed that visfatin enhanced the estrogen response element (ERE)-dependent activity
of ER in the presence of 17-β estradiol (E2). Additional study on T47D cells showed that visfatin also increased
Ser118 and Ser167 phosphorylation of ERα and enhanced ERE-dependent activity in the presence of E2
in these cells.
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Keywords
Breast cancer, Estrogen receptor, Serine 118 phosphorylation, Serine 167 phosphorylation, Visfatin
Citation
EXCLI Journal 2018;17:516-525