Membrane-initiated estradiol signaling of epithelial-mesenchymal transition-associated mechanisms through regulation of tight junctions in human breast cancer cells.

Autor: Jiménez-Salazar JE; Department of Biology of Reproduction, Universidad Autonoma Metropolitana (UAM), 09310, Mexico City, Mexico., Posadas-Rodríguez P, Lazzarini-Lechuga RC, Luna-López A, Zentella-Dehesa A, Gómez-Quiroz LE, Königsberg M, Domínguez-Gómez G, Damián-Matsumura P
Jazyk: angličtina
Zdroj: Hormones & cancer [Horm Cancer] 2014 Jun; Vol. 5 (3), pp. 161-73. Date of Electronic Publication: 2014 Apr 26.
DOI: 10.1007/s12672-014-0180-3
Abstrakt: Tumor cells utilize inappropriate epithelial-mesenchymal transition (EMT) mechanisms during the invasive process. It is becoming increasingly clear that estradiol (E2) induces breast cancer cell progression and enhances EMT; however, the mechanisms associated with this are unclear. We investigated the role of E2 on the expression and intracellular localization of the tight junction (TJ)-associated proteins, zonula occluden 1 (ZO-1), ZO-1-associated nucleic acid binding (ZONAB), and occludin, on the activation of c-Src and human epidermal growth factor receptor 2 (HER2) expression and cellular migration in the estrogen receptor (ER)-positive breast cancer cell lines, MCF-7 and T47D. We demonstrated that 1 nM E2 elicits c-Src activation after 15 min. The p-Src/ZO-1 complex led to ZO-1 and ZONAB disruption at the TJ and increased expression of HER2 mRNAs. These changes correlate with decreased expression of the epithelial markers occludin and CRB3 and increased synthesis of N-cadherin. This led to increased MCF-7 cell migration induced by E2, even in the presence of a cell proliferation inhibitor. Incubation with ICI 182,780 (Fulvestrant), an ER antagonist, precluded the effects of E2 on c-Src phosphorylation, p-Src/ZO-1 complex formation, ZO-1/ZONAB nuclear translocation, and migration of MCF-7 cells. Our findings suggest that E2 promotes TJ disruption during tumor progression and increases cell motility. We propose a novel pathway where estrogens promote EMT-associated mechanisms that possibly lead to metastasis.
Databáze: MEDLINE
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