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

Authors

  • Mohammad Zangooei Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Mitra Nourbakhsh Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  • Mohammad Hossein Ghahremani Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  • Reza Meshkani Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Azam Khedri Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Amir Shadboorestan Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  • Hajar Shokri Afra Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Shiva Shahmohamadnejad Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Hossein Mirmiranpour Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Shahnaz Khaghani Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

DOI:

https://doi.org/10.17179/excli2018-1299

Keywords:

breast cancer, estrogen receptor, Serine 118 phosphorylation, Serine 167 phosphorylation, visfatin

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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Published

2018-06-04

How to Cite

Zangooei, M., Nourbakhsh, M., Ghahremani, M. H., Meshkani, R., Khedri, A., Shadboorestan, A., … 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

Issue

Vol. 17 (2018)

Section

Original articles

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