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In vivo quantitative proteomics to study skin cancer progression

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A two-stage skin carcinogenesis mouse model, the SILAC mouse1 and high-resolution mass spectrometry were combined to investigate defects in regulatory circuits in cutaneous carcinoma. In depth analysis of the proteome and phosphoproteome of normal skin, TPA -treated skin, papilloma and squamous cell carcinoma was performed. This approach led to the identification of more than 6,000 proteins and 13,000 phosphorylation sites. Quantitative analysis revealed regulation of proteins known to play a role in carcinoma development. As expected, protein substrates for MAP Ks and CDKs were highly phosphorylated, providing a positive control, but the vast majority of phosphorylation changes are novel. We conclude that our quantitative in vivo (phospho) proteomic approach is a powerful strategy to discover new molecules in carcinoma development for further elucidation.

1Krüger M, Moser M, Ussar S, Thievessen I, Luber CA, Forner F, Schmidt S, Zanivan S, Fässler R, Mann M. Cell. 2008 Jul 25;134(2):353-64.

This talk is part of the Cancer Research UK Cambridge Institute (CRUK CI) Seminars in Cancer series.

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