Abstract 4341: Metabolomic analysis of HER2-positive breast cancer cells

Abstract

Abstract Purpose: HER2-positive breast cancer accounts for more than 20% of the diagnosed cases and is characterized by aggressive growth, increased disease recurrence, and poor prognosis. While much of the signaling mechanism(s) have been elucidated, the impact of HER2 positivity on cellular metabolism is not well understood. We examined (1) gene expression profiles of mammalian breast cancer cell lines with increasing HER2 expression levels (MCF10A, MDA-MB-468, MDA-MB-453, HCC1954, HCC2218) and correlated changes to metabolic expression profiles and (2) the effect of serum starvation and pervanadate treatment on the metabolic profiles of these HER2-expressing cell lines. Methods: Our study used a combination of 1H-NMR and 2D-NMR (TOCSY), bioinformatics analyses, and protein expression validation in human breast cancer cell lines (untreated, serum-starved, serum-starved with pervanadate treatment). Results: We found that both gene and metabolic expression profiles of HER2-positive cell lines correlated with leucine and isoleucine biosynthesis (p-value < 0.05). Comparative analyses of profiles from untreated, serum-starved, and serum-starved with pervanadate-treated cell samples revealed that lactate concentration (p-value <0.05) dropped significantly with serum starvation and pervanadate treatment consistent with reduced glycolytic metabolism and potentially mediated through suppression of tyrosine phosphatase activity. Conclusion: This study highlights important new metabolites that are potential biomarkers of HER2-positive breast cancer and suggests alternate/novel pathways to consider for future understanding and treatment. Citation Format: Malika K. Sahni, Resmi K. Ravindran, Imran H. Khan, Jason A. Bush, V. V. Krishnan. Metabolomic analysis of HER2-positive breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4341. doi:10.1158/1538-7445.AM2014-4341