Chronic Exposure to Low Levels of Parabens Increases Mammary Cancer Growth and Metastasis in Mice

Methylparaben (MP) and propylparaben (PP) are commonly used as food, cosmetic, and drug preservatives. These parabens are detected in the majority of US women and children, bind and activate estrogen receptors (ER), and stimulate mammary tumor cell growth and invasion in vitro. Hemizygous B6.FVB-Tg (MMTV-PyVT)634Mul/LellJ female mice (n =20/treatment) were exposed to MP or PP at levels within the US Food and Drug Administration's “human acceptable daily intake.” These paraben-exposed mice had increased mammary tumor volume compared with control mice (P< 0.001) and a 28% and 91% increase in the number of pulmonary metastases per week compared with the control mice, respectively (P< 0.01). Indeed, mammary tumors from PP-exposed mice had an increased retention of introns (P< 0.05). Our data suggest that parabens cause substantial mammary cancer metastasis in mice as a function of their increasing alkyl chain length and highlight the emerging role of aberrant spliceosome activity in breast cancer metastasis. Overall design: RNA-seq was conducted for 59 primary mammary tumors (19 from vehicle group, 20 from methylparaben group, and 20 from propylparaben group)