Proteomic profiling of Trastuzumab (Herceptin(R))-sensitive and -resistant SKBR-3 breast cancer cells.
- Autori: DI CARA, G.; Marengo, G.; Albanese, N.; Marabeti, M.; Musso, R.; Cancemi, P.; Pucci, I.
- Anno di pubblicazione: 2013
- Tipologia: Articolo in rivista (Articolo in rivista)
- Parole Chiave: Trastuzumab, Herceptin(R), Breast Cancer, Proteomics
- OA Link: http://hdl.handle.net/10447/71272
BACKGROUND: The Human Epidermal Growth Factor Receptor 2 (HER-2), overexpressed in 25-30% of breast carcinomas (BC), is the therapeutic target for trastuzumab, a recombinant humanized monoclonal antibody. The initial response to trastuzumab is often followed by drug-insensitivity within one year. Several hypotheses have been raised to explain this event, but the mechanisms behind the responses to trastuzumab are still unclear. Aim: To study the effects of short and prolonged trastuzumab treatment on the proteomic profiles of HER-2-overexpressing SKBR-3 BC cells. MATERIALS AND METHODS: Cells were treated with trastuzumab to obtain sensitive and resistant clones. The drug effects were evaluated at the phenotypical and proteomic levels. RESULTS: In the trastuzumab-resistant cells the expression of a large amount of proteins, initially affected by treatment, reverted to levels of the untreated cells. CONCLUSION: The results obtained so far illustrate for the first time a large-scale differential protein expression between trastuzumab-treated and untreated cells, and between trastuzumab-sensitive and resistant cells. We believe that the results obtained will help to increase the knowledge of the molecular effects of trastuzumab and will be useful to better-understand the drug resistance mechanisms.