Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP16-Cancers of Endocrine Organs: Mechanisms of Tumorigenesis & Progression
Sunday, June 16, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 11:00 AM
Room 206 (Moscone Center)

Poster Board SUN-292
Javier E. Jiménez-Salazar*1, Pedro Posadas-Rodriguez1, Roberto C. Lazzarini-Lechuga1, Armando Luna-López2, Luis Enrique Gómez-Quiroz1, Mina Königsberg1, Alejandro Zentella3 and Pablo Damian-Matsumura1
1Universidad Autónoma Metropolitana (UAM), Mexico City, Mexico, 2National Institute of Geriatrics, Mexico City, Mexico, 3National Institute of Medical Sciences and Nutrition, Mexico City, Mexico
The process of epithelial-mesenchymal transition (EMT) is increasingly viewed as a significant clinical problem in cancer, as EMT is thought to promote an aggressive cancer stem cell phenotype, therapy resistance, and metastasis. It has been shown that estradiol (E2) promotes breast cancer cell progression and can enhance EMT; however, the detailed mechanisms remain 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), ZONAB (ZO-1-associated nucleic-acid-binding protein) and occludin, on the activation of the tyrosine-protein kinase Src and the epidermal growth factor receptor-2 (HER-2);  cell permeability and migration were also measured on the human breast cancer cell line MCF-7.

We demonstrated that E2 (10-9M) elicits Src activation (Tyr-416 phosphorylation) after 15 min incubation. Subsequently, the p-Src/ZO-1 complex led to ZO-1 and ZONAB disruption at the TJ and to their nuclear translocation after 30 min of E2 incubation. HER-2-mRNA and protein expression increased after 3 h and 24 h respectively, since it has been shown that ZO-1 and ZONAB regulate this tyrosine kinase receptor expression. These changes correlated with decrease expression (Westen blot and immunofluorescence studies) of epithelial markers occludin (adhesion marker) and CRB3 (polarity marker), and increased the mesenchymal marker N-cadherin synthesis. These effects led to increased paracellular permeability (measured by FITC-Dextran intake) and MCF-7 cell migration (measured by the wound healing technique) induced by E2.

The incubation with an estrogen receptor antagonist (ICI 182,780) precluded Src phosphorylation, p-Src/ZO-1 complex formation, ZO-1/ZONAB nuclear translocation, increased permeability and cell migration of MCF-7 cells.

These studies strongly suggest that during tumor progression, E2 promotes TJ disruption, nuclear translocation, gene expression regulation, permeability increase and breast cancer ER-positive invasion, therefore our results have identified a novel pathway in which estrogens promote EMT as a process leading to metastasis.

Nothing to Disclose: JEJ, PP, RCL, AL, LEG, MK, AZ, PD

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Acknowledgments: We are thankful for the technical support of the Confocal microscopy (R. Lazzarini) and Molecular Biology (A. Serrato) laboratories staff of DCBS-UAM. This study was supported by DCBS-UAM and the ICYTDF-UAM Nanotechnology project. JEJ-S and PP-R are CONACYT's scholarships recipients and are enrolled in the Experimental Biology Graduate Program (212870), UAM, MEXICO.