Investigating the effect of visfatin on ERalpha phosphorylation (Ser118 and Ser167) and ERE-dependent transcriptional activity

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Mohammad Zangooei
Mitra Nourbakhsh
Mohammad Hossein Ghahremani
Reza Meshkani
Azam Khedri
Amir Shadboorestan
Hajar Shokri Afra
Shiva Shahmohamadnejad
Hossein Mirmiranpour
Shahnaz Khaghani

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. Visfatin-induced 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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How to Cite
Zangooei, M., Nourbakhsh, M., Ghahremani, M. H., Meshkani, R., Khedri, A., Shadboorestan, A., Shokri Afra, H., Shahmohamadnejad, S., Mirmiranpour, H., & Khaghani, S. (2018). Investigating the effect of visfatin on ERalpha phosphorylation (Ser118 and Ser167) and ERE-dependent transcriptional activity. EXCLI Journal, 17, 516-525. https://doi.org/10.17179/excli2018-1299
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Original articles

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