Benzo-[a]-pyrene increases invasion in MDA-MB-231 breast cancer cells via increased COX-II expression and prostaglandin E2 (PGE2) output.

Benzo-[a]-pyrene (B[a]P), a carcinogenic component of cigarette smoke, has been shown to increase both COX-II expression and prostaglandin output in vascular smooth muscle and oral epithelial cells. In addition, invasive breast cancer cells have been reported to over express COX-II and PGE(2). Therefore, the objective of this study was to quantify the effect of increasing B[a]P concentrations on COX-II expression, PGE(2) output, and invasion using MDA-MB-231 cells, an invasive estrogen unresponsive breast cancer cell line. B[a]P significantly increased invasion in MDA-MB-231 cells at concentrations greater than 4 x 10(-8) M. Treatment of MDA-MB-231 cells with Vomitoxin (a selective COX-II inducer) enhanced invasion whereas co-treatment with NS398 (a selective COX-II inhibitor) attenuated B[a]P-induced invasion in MDA-MB-231 cells. Immunohistochemical staining and Western blots demonstrated a significant B[a]P treatment-induced increase in both the number of COX-II immunopositive MDA-MB-231 cells and COX-II protein levels. Moreover, B[a]P-treatment induced a profound (46 fold) increase in PGE(2) production by MDA-MB-231 cells. The aryl hydrocarbon receptor (AhR) antagonists resveratrol (RES) and alpha-naphthaflavone (alpha-NF) had no effect on their own, whereas B[a]P-induced invasion was significantly inhibited by co-treatment with RES and alpha-NF. Our data demonstrate that B[a]P-induced changes in invasion are mediated through augmented COX-II expression and PGE(2) production involving an AhR regulated pathway. Moreover, these results suggest a potential role for the AhR signalling pathway in breast cancer invasion.