ICEECE2012 Poster Presentations Nuclear receptors and Signal transduction (17 abstracts)
1Metropolitan Autonomous University, Mexico City, Mexico; 2Geriatric institute, Mexico City, Mexico; 3National Institute of Medical Sciences and Nutrition, Mexico City, Mexico; 4National Autonomous University, Mexico City, Mexico.
Tight junctions (TJ) exist as macromolecular complexes comprised of several types of membrane proteins, cytoskeletal proteins and signaling molecules. Recently, it has been observed that some components are regulated during epithelialmesenchymal transition in cancer cells; however, the effects of estradiol (E2) have been poorly studied. This study sought to determine the role of E2 on the expression and cell localization of the TJ-associated proteins Zonula Occluden-1 (ZO-1), occludin and the ZO-1-associated transcription factor (ZONAB), and in the activation of the epidermal growth factor receptor-2 (HER-2) and Rous sarcoma virus (SRC), in the human breast cancer cell line MCF-7. We demonstrated that E2 increases ZO-1 and ZONAB mRNA and protein expression after 6 h of incubation, and HER-2 after 24 h. Since it is known that ZO-1 and ZONAB act as co-activator and transcription factor respectively, in the promoter of the HER-2 gene, immunolocalization assays (Western blot and confocal microscopy) were performed. After 30 min of incubation with E2, maximal translocation of ZO-1 and ZONAB proteins to cell nucleus was observed. This effect was not precluded when an estrogen receptor (ER) antagonist was used; therefore, ZO-1 and ZONAB protein translocation can be associated to SRC protein, since active SRC increased significantly after E2 incubation. We also demonstrated that E2 decreased dramatically occluding levels in MCF-7 cells, effect that can be associated with an increase in paracellular permeability. We conclude that E2 can induce genomic and non-genomic changes in TJ proteins that induce epithelial-mesenchymal transition and cell proliferation in breast cancer cells.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported however funding details unavailable.