Aim: 

Bisphenol A (BPA) is the prototype of environmental endocrine disruptors (EDs) which interfere with natural hormones at concentrations below its toxicity threshold. BPA acts as a mitogenic substance and it was thought that the estrogen receptor a subtype (ERa) is the foremost molecular mediator of BPA-induced proliferation. However, two ER subtypes exist which elicit opposite 17b-estradiol (E2)-induced effects on human physiology: ERa principally mediates the proliferative properties of E2, whereas ERb is responsible for the antiproliferative effects of E2.

Methods: 

Here, the mechanism(s) of BPA to induce cell proliferation in different human cancer cell lines transfected with ERa expression vector (HeLa cells) or expressing endogenous ERb (DLD-1 cells) is reported.

Results: 

Similarly to E2, BPA promotes HeLa cell proliferation via ERa-dependent signal transduction pathways. On the other hand, although in vitro BPA binds ERa and ERb with comparable affinity, in ERb containing cancer cells BPA stimulation completely impairs the proapoptotic cascade triggered by E2. As a whole, BPA acts as an E2 mimetic in the presence of ERa enhancing cancer cell proliferation and as an E2 antagonist in the presence of ERb abolishing the protective effect elicited by E2.

Conclusion: 

A more complex molecular mechanisms underlie the ED action of BPA on cancer cell growth.