Regulation of the EGF receptor by dibutyl phthalate

Di-n-butyl phthalate (DBP) is a phthalate ester formed by the reaction of n-butanol with phthalic anhydride.  DBP is commonly found in latex adhesives, cellulose acetate plastics, dyes, personal care products, and the enteric coating of some oral medications.  DBP is an environmental chemical of interest because it can be released to the environment during its production and incorporated into products, as well as from products themselves as they are used and disposed.  DBP is a chemical of concern in the study of breast cancer because it has been shown to bind and activate the estrogen receptor alpha (ESR1), and important factor that stimulates growth of a large proportion of breast cancers.  DBP has also been shown to promote growth and inhibit tamoxifen-induced apoptosis in MCF-7 human breast cancer cells.  Although no epidemiological data is available demonstrating an association between DBP and breast cancer, these data exist for a similar phthalate, diethyl phthalate. The working hypothesis for this pilot project is that DBP synergizes with EGF to activate the EGF receptor in breast cancer cells and the effects of DBP are dependent on estrogen. The proposed experiments are collaborative in the Vaillancourt and Craig laboratories and will result in the publication of at least one manuscript.  An R01 grant application will follow incorporating both the cell-based studies with the mouse studies.