Proteomic characterization of novel alternative splice variant proteins in human epidermal growth factor receptor 2/neu-induced breast cancers.

Multifaceted alternative splicing in cancer cells greatly diversifies protein structure independently of genome changes, but the characterization of cancer-associated splice variants is quite limited. In this study, we used mass spectrometric data to interrogate a custom-built database created with three-frame translations of mRNA sequences from Ensembl and ECgene to find alternative splice variant proteins. In mass spectrometric files from liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses of normal mouse mammary glands or mammary tumors derived from conditional human epidermal growth factor receptor 2 (Her2)/neu transgenic mice, we identified a total of 608 alternative splice variants, of which peptides from 216 proteins were found only in the tumor sample. Among the 608 splice variants were 68 novel proteins that were not completely matched to any known protein sequence in mice, for which we found known functional motifs. Biological process enrichment analysis of the splice variants identified suggested the involvement of these proteins especially in cell motility and translation initiation. The cancer-associated differentially expressed splice variant proteins offer novel biomarker candidates that may function in breast cancer progression or metastasis. (c)2010 AACR.