title: Signalling pathways involved in endocrine resistance in breast cancer and associations with epithelial to mesenchymal transition (Review).
abstract: Both de novo and acquired endocrine resistance constitute a major therapeutic problem for treatment of hormone-positive breast cancer. Multiple explanatory mechanisms have been proposed through the study of cellular models which focus principally on receptor tyrosine kinase mediated signalling pathways utilizing src, PI3K, MAPK and Smads. Many of the transducing molecules, particularly nuclear transcription factors such as Snail, Twist, Snail2, ZEB, FOXC2, TCF/LEF and Goosecoid are participants in proliferation as well as invasion and metastasis, involving a process of orchestrated cellular remodeling which is being likened to the process of epithelial to mesenchymal transition that takes place during embryonic development. We review the accumulating evidence that points towards the occurrence of this phenomenon as a consequence of the loss of endocrine control, with both processes being similarly characterized by depletion of cell adhesion proteins, E-cadherin, catenins and cytokeratins, increased association with the extracellular matrix through induction of metalloproteinases, fibronectin and collagen, and a switch to a mobile vimentin-based cytoskeletal structure with loss of apical basal polarity.
authors.affiliation: Faculty of Pharmacy ,University of Kuwait, PO Box 24923, Safat 13110, Kuwait.
authors.forename: Sanaa
authors.initials: S
authors.lastname: Al Saleh
authors.forename: Leyla H
authors.initials: LH
authors.lastname: Sharaf
authors.forename: Yunus A
authors.initials: YA
authors.lastname: Luqmani
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000502:physiology; D005260:Female; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011960:Receptors, Estrogen / Q000502:physiology; D015398:Signal Transduction; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D003598:Cytoskeletal Proteins; D011960:Receptors, Estrogen; D013629:Tamoxifen; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors