Forkhead transcription factor FOXO1 inhibits nuclear factor‐κB in gastric cancer

Abstract

FOXO1, a forkhead box O (FOXO) transcription factor, and nuclear factor-κB (NF-κB) are prognostically significant transcription factors in gastric cancer. As their relationship has been inconsistent depending on the cell type, we aimed to investigate whether FOXO1 is associated with NF-κB p65 (RelA) in gastric cancer. Immunohistochemistry was performed on tissue array slides containing 298 gastric carcinoma specimens. We found that the cytoplasmic expression of pFOXO1, the inactive form of FOXO1, was positively correlated with nuclear RelA expression (p=0.024). In addition, the expressions of pFOXO1 and RelA were positively related with cyclin D1 expression (p=0.014 and p=0.001, respectively) and Ki-67 labeling index (p=0.025 and p=0.017, respectively). However, they did not show association with the expressions of cyclin E, p53 and pRb. Cell culture experiments showed that FOXO1 overexpression by transfection of FOXO1 AAA mutant gene suppressed NF-κB activation in SNU-484 gastric cancer cells. These results suggest that FOXO1 and NF-κB are negatively associated and that FOXO1 is a negative upstream regulator of NF-κB in gastric cancer.