Quantitative assessment of endogenous retinoids in breast cancer models

Abstract

Breast cancer pathogenesis involves disregulation of signaling by retinoic acid (RA), the active metabolite of vitamin A and an essential regulator of cell proliferation, differentiation, and apoptosis. It is not clear if changes to endogenous RA concentrations (via RA biosynthesis defects) or changes to proteins that translate the RA signal drive physiological outcomes. We are interested in understanding if endogenous RA levels are altered in tumors and, if so, when does disregulation of RA concentrations occur during carcinogenesis. From evaluations of gene expression of various components of the retinoid pathway, disregulation of RA signaling is an early event in cancer making the retinoid pathway is an attractive metabolic target for intervention and chemoprevention. Altered expression of genes involved in the trafficking of retinoids is indirectly linked to RA synthesis defects with the implication that RA synthesis defects exacerbate tumor progression. However, there has been no direct quantification of endogenous RA to characterize if RA is altered and, if so, the extent of the alteration. Here we describe quantitative mass spectrometric approaches for quantifying endogenous RA and other retinoids in tissue and present data from models used to study mammary carcinoma.