Session: FP16-Cancers of Endocrine Organs: Mechanisms of Tumorigenesis & Progression
Room 206 (Moscone Center)
Poster Board SUN-292
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
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