Nous mecanismes de resistència primària al trastuzumab (Herceptin)bases moleculars per a la determinació d'un nou subtipus de càncer de mama (Basal/ErbB2+)
- Oliveras Ferraros, C.
- Rafael de Llorens Duran Directeur/trice
Université de défendre: Universitat de Girona
Fecha de defensa: 21 juin 2013
- Ander Urruticoechea Ribate President
- Antoni Benito Mundet Secrétaire
- Luciano Vellón Rapporteur
Type: Thèses
Résumé
The aim of this doctoral thesis was to unravel mechanisms underlying primary resistance to trastuzumab regarding a putative new breast cancer subtype with mixed basal & ErbB2+ molecular features. Using the JIMT-1 breast cancer cell line as a model, we have been able to identify several candidate mechanisms responsible for trastuzumab resistance in basal/ErbB2+ breast cancer cells: 1) overexpression of survivin, an inhibitor of apoptosis protein family member; 2) Overactivation and sub-cellular re-localization of IGF-1R, a growth factor receptor involved in cellular proliferation and metastasis; and 3) Over-representation of breast cancer cells bearing the CD44+CD24-/low mesenchymal phenotype, which are enriched with putative breast cancer stem cells (CSCs) due to the activation of epithelia-to-mesenchymal transition (EMT) phenomena