Characterisation of ErbB2 mediated signalling events in breast cancer
The tyrosine kinase receptor ERBB2/HER2 is amplified in a significant proportion of human breast cancers, where it is correlated to poor prognosis for the patient. Due to its central role in the development of breast cancers, a thorough understanding of the ERBB2 signalling network has emerged as a key component to developing more effective treatments. The Cancer Proteomics Group has previously conducted protein and gene expression profiling of cell models and breast tissues and identified poorly characterised gene products potentially associated with ERBB2-dependent transformation. Further investigation of such unknown components of the ERBB signalling network, may yield novel biomarkers. My research aims to elucidate the role of select candidates previously identified by the Timms laboratory, namely CPNE3, AGR2, STARD10 and ERRB2. These target candidates are hypothetically associated with ERBB2-dependent cellular transformation; however, little is known of their role in downstream signalling of ERBB2. Hence, the project seeks to sequentially elucidate the role of the target genes in ERBB2 signalling. This will be achieved by assessing the effect of siRNA mediated knockdown on adhesion, invasion, and proliferation in ErbB2 over-expressing breast cancer cell lines. In addition, global protein expression analysis will be conducted using a combination of tandem mass tags and liquid chromatography tandem mass spectrometry (TMT-LC-MS/MS).
Dr John Timms