INVESTIGATING THE EFFECT OF VISFATIN ON ERa PHOSPHORYLATION (SER118 AND SER167) AND ERE-DEPENDENT TRANSCRIPTIONAL ACTIVITY.

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

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 (ERa) is also associated with carcinogenesis. The activity of ERa 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 ERa in MCF-7 breast cancer cells. We showed that exogenous administration of visfatin significantly increased the phosphorylation of ERa 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 ERa. We also showed that visfatin enhanced the estrogen response element (ERE)-dependent activity of ER in the presence of 17-ß estradiol (E2). Additional study on T47D cells showed that visfatin also increased Ser118 and Ser167 phosphorylation of ERa and enhanced ERE-dependent activity in the presence of E2 in these cells.

OBESITY; PHOSPHORYLATION; GENETIC transcription; BREAST cancer treatment; ESTROGEN receptors; DISEASE incidence

EXCLI Journal, 2018, Vol 17, p516

1611-2156

Academic Journal

10.17179/excli2018-1299