Adipocytes from obese subjects increase NF‐kB activation in invasive breast cancer cells

Abstract

Obesity in post‐menopausal women doubles the breast cancer risk and metastasis. Concomitantly, nuclear factor kappa B (NF‐κB) is known to play a significant role in breast cancer cell metastasis. We used a novel three dimensional (3D) co‐culture system with breast cells (non‐cancerous, MCF10A, cancerous, MCF7 and invasive, MDA231) and adipocytes from pre‐ and post‐menopausal women in lean and obese groups. Comparison of cytokine profiles of co‐cultures revealed two‐way interaction of adipocytes and breast cells. Highly significant cytokine changes were reported for post‐menopausal adipocytes and MDA MB 231 co‐culture. Therefore, we assayed the NF‐κB activation effects of lean and obese post‐menopausal adipocytes on MDA MB 231 cells. Media transfer from lean/obese post‐menopausal adipocyte cultures in to growing MDA MB 231 breast cells resulted significant changes in NF‐κB activation pathway genes. This further verified our previous data that obese conditioned media increased the levels of NF‐κB family members (P65, P50, P52, Rel B and Rel C) compared to the lean counterpart. Therefore, our data indicates that adipocytes from post‐menopausal obese women can increase the NF‐κB activation in MDA MB 231 cells. In conclusion, this study suggests that increased breast cancer risk in obese post‐menopausal women may be at least in part due to obesity mediated NF‐κB activation. Support: UTORC, AgResearch and UTGSM.Grant Funding Source : Internal