Arachidonic acid enhances TNF-α-induced tumorigenesis in human breast cancer cell line and rat mammary tumors.

Abstract Background: Our group has previously reported that arachidonic acid (AA, 20:4n-6) levels are 10 times higher in rat mammary tumor tissue compared to the normal mammary gland. Nuclear factor kappaB (NF-κB) activation is often found to be constitutive in human breast cancer, showing higher activation in the more aggressive subtypes. Methods : We incubated the human breast cancer MCF-7 cells for 48 h, in medium supplemented with BSA or BSA-bound 10, 50 and 100 mM AA, then added the same medium alone or supplemented with 10 ng/mL TNF-α. Thirty carcinogen-induced rat mammary tumors, weighting between 0.3 g and 19.2 g, were examined. Results : The carcinogen-induced rat mammary tumor weight was positively correlated with AA level, p-Akt/Akt ratio, nuclear p65, c-Myc and VEGF expression. In MCF-7 cells, AA alone had no effect on NF-kB activation. However, 50 or 100 μM AA pretreatment enhanced TNF-α-induced p-Akt/Akt, and p-IkB expression, with subsequent decrease in IkB. Thereafter, an increase in nuclear p65, nuclear c-Myc expression, NF-kB gene reporter activity and cell proliferation was observed. Conclusion : AA can effectively augment p-Akt signaling and TNF-α-induced NF-kB activation to promote the tumorigenesis in breast cancer. Our study indicates that AA may influence tumor progression by increasing the aggressiveness of breast cancer.