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Proteomic characterization of novel alternative splice variant proteins in human epidermal growth factor receptor

Rajasree Menon1, Gilbert S Omenn

  • 1Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109-2218, USA. rajmenon@umich.edu

Cancer Research
|April 15, 2010
PubMed

Insights

Researchers identified 608 alternative splice variants, including 68 novel proteins, in mouse breast tumors. These cancer-associated splice variants, particularly those involved in cell motility, may serve as potential biomarkers for breast cancer progression and metastasis.

Area of Science:

  • Proteomics
  • Cancer Biology
  • Molecular Biology

Background:

  • Alternative splicing diversifies protein structure in cancer independently of genomic alterations.
  • Characterization of cancer-associated splice variants remains limited, hindering understanding of their roles.

Purpose of the Study:

  • To identify and characterize alternative splice variant proteins in breast cancer using mass spectrometry.
  • To investigate the functional implications of these splice variants in tumor development.

Main Methods:

  • Utilized mass spectrometric data (LC-MS/MS) from normal and Her2/neu transgenic mouse mammary tumors.
  • Interrogated a custom-built database with three-frame translations of mRNA sequences from Ensembl and ECgene.
  • Identified splice variants and novel proteins, analyzing their functional motifs and biological processes.

Main Results:

  • Identified a total of 608 alternative splice variants in mouse mammary glands and tumors.
  • Found peptides from 216 proteins exclusively in tumor samples.
  • Discovered 68 novel proteins lacking complete matches in known mouse sequences, possessing known functional motifs.
  • Biological process analysis indicated involvement in cell motility and translation initiation.

Conclusions:

  • Cancer-associated differentially expressed splice variant proteins were identified.
  • These variants, particularly those linked to cell motility, represent potential novel biomarkers for breast cancer progression and metastasis.

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