Bisphenol A impairs estradiol-induced protective effects against DLD-1 colon cancer cell growth.

ABSTRACT

Bisphenol A (BPA), a prototype of endocrine disruptors, mimics 17ß-estradiol (E2)-induced proliferation in several cancer cells by binding to estrogen receptor α (ERα). However, scarce and conflicting data are available concerning the effect of BPA on estrogen receptor ß (ERß)-mediated functions. Here, the detailed analysis of the effect of BPA, alone or in combination with E2, on ERß-mediated cellular functions is reported in ERß-expressing colon cancer cell line. BPA binds to ERß without activating any receptor activities. On the other hand, BPA inhibits E2-induced genomic activity of ERß as well as ERß extra-nuclear activities (i.e., ERßp38 association and p38 activation). As a consequence, BPA impairs the E2-induced activation of the apoptotic cascade which is at the root of the protective role played by the hormone against colon cancer growth. Thus, women may be considered a highly susceptible population with an increased risk of colon cancers after BPA exposures.