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Title: Analysis of ErbB2- and growth factor-dependent gene expression in breast cells
Author: Bertani, Mariana Fianco
ISNI:       0000 0001 3462 0687
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2006
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The ErbB family of growth factor receptors are important mediators of cellular signalling that control changes in an array of cellular responses such as proliferation, differentiation, migration, adhesion and apoptosis through the activation of various downstream signalling pathways. The ErbB family of receptor tyrosine kinases includes four members EGFR (ErbBl), ErbB2, ErbB3 and ErbB4. ErbB2 is an important target for breast cancer therapy because it is overexpressed by gene amplification in 25 to 30% of all breast cancers and was the target of the first successful therapeutic monoclonal antibody. Because of its clinical importance, understanding the role of ErbB2 and other members of the ErbB receptor family in cancer has been the subject of intense research. However, although much is now known about the signalling pathways activated downstream of the ErbB family members, the mechanisms involved in ErbB2-mediated tumourigenesis are still poorly understood. The purpose of this study was to understand the underlying changes associated with ErbB2-dependent signalling and transformation. The major part of this study was focused on deciphering global changes in gene expression associated with ErbB2 overexpression and was analysed by microarray technology using a model human mammary luminal epithelial cell system. In addition, differential gene expression associated with downstream signalling events activated by two ErbB-specific ligands, EGF and HRG, were examined. Microarray analysis allowed the identification of potential molecular markers of ErbB2 overexpression, some of which have been previously implicated in breast or other types of cancer. Gene expression changes for a number of genes were validated by quantitative real-time PCR, and a number of genes were further validated at the protein level. Subsequently, members of a growth-regulatory signal transduction pathway involving interferon signalling found to have altered gene expression due to ErbB2 overexpression were further characterised, and their connection with ErbB2-depedent signalling and transformation investigated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available