Micro-RNA Signature of the Epithelial-Mesenchymal Transition in Endometrial Carcinosarcoma.
Maria Angeles Castilla, Gema Moreno-Bueno, Laura Romero-Perez, Koen Van De Vijver, Michele Biscuola, Maria Angeles Lopez-Garcia, Jaime Prat, Xavier Matias-Guiu, Amparo Cano, Esther Oliva, Jose Palacios. Hospital Universitario Virgen del Rocio-IBIS, Sevilla, Spain; Instituto de Investigaciones Biomédicas "Alberto Sols" (CSIC-UAM), IdiPAZ (Instituto de Investigación La Paz), Madrid, Spain; Massachusetts General Hospital, Boston; Hospital San Pau, Barcelona, Spain; Hospital Universitari Arnau de Vilanova, Lleida, Spain
Background: Endometrial carcinosarcomas (ECS) are human neoplasias that undergo a true epithelial mesenchymal transition (EMT). The molecular determinants of the EMT in human tumours in vivo are still to be fully established, although a role for some miRNAs in EMT was recently suggested from in vitro cellular models, mainly involving the miR-200 family. The aim of this study was to analyze the microRNA (miRNA) signatures associated to EMT in human carcinosarcomas, and to determine their relationships with EMT markers and repressors of E-cadherin transcription.
Design: The expression of E-, P-, and N-cadherin, cadherin-11, p120, vimentin, SPARC, fascin and caveolin-1 was studied in a group of 76 ECS by immunohistochemistry. Real-time PCR was used to measure differences in the expression of 384 miRNAs, E-cadherin, Cadherin-11, SPARC, SNAIL,ZEB1, ZEB2, TWIST-1, TCF4, TGFß1 and TGFß2 between the epithelial and mesenchymal component of 23 ECS.
Results: A loss of epithelial characteristics, including cadherin switching and the acquisition of a mesenchymal phenotype, was accompanied by changes in the profile of miRNA expression and the upregulation of all the E-cadherin repressors analyzed. There was a more than 5-fold difference in the expression of 14 miRNAs between both neoplastic components. Members of the miR-200 family are involved in epithelial differentiation and they were downregulated in the mesenchymal part of the ECS. In addition, miR-23b, miR-29c, which are involved in the inhibition of mesenchymal markers, and miR-203 that is involved in the inhibition of cell stemness, were also downregulated. Upregulated miRNAs included miR-155, miR-369-5p, miR-370, miR-450a and miR-542-5p.
Conclusions: These data suggest that in human ECS, the interplay between transcriptional repressors of E-cadherin and miRNAs provides a link between EMT-activation and the maintenance of stemness. Supporting by grants from: ISCIII: PI07/90324, PI 080971; RD06/0020/0013; PI-0384/2007 and Proyecto de Excelencia P07-CVI-03100.
Category: Gynecologic & Obstetrics
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 179, Wednesday Afternoon