Identification of breast cancer biomarkers in transgenic mouse models: A proteomics approach

Purpose: Transgenic mouse models for cancer circumvent many challenges that hamper human studies aimed at biomarker discovery. Lower biological variances among mice combined with controllable factors such as food uptake and health status may enable the detection of more subtle protein expression differences. This is envisioned to result in the identification of biomarkers better discriminating cancer cases from controls.

Experimental design: The current study used two innovative mouse models for breast-cancer to identify new serum biomarkers. Multi-analyte profiling technique was used to analyze 70 proteins in individual serum samples of non-tumor and mammary tumor-bearing Tg.NK (MMTV/c-neu) mice.

Results: A small set of proteins fully differentiated tumor samples from controls. These comprised osteopontin, interleukin-18, cystatin C and CD40 antigen. Comparison of protein expression in another breast-cancer mouse model, the humanized p53.R270H mice, showed common discriminatory expression of osteopontin. However, other biomarkers showed distinct expression in the two different breast-cancer models, indicating that different mammary tumor sub-types with respect to molecular and estrogen receptor status reveal divergent serum biomarker sets.

Conclusions and clinical relevance: The current study supports the concept that serum proteins can discriminate mammary tumor cases from controls, and yielded interesting biomarkers that need further testing and validation in human studies.