Forkhead transcription factor FOXO1 inhibits nuclear factor‐κB in gastric cancer |
| |
| Authors: | Da‐Ae Yu Jiyeon Yoon Young San Ko Jinju Park Sue Youn Kim Min A Kim Ji Hun Kim Jieun Jung Younghee Cheon Hye Seung Lee Woo Ho Kim Byung Lan Lee |
| |
| Affiliation: | 1. Department of Anatomy, Seoul National University College of Medicine, , Seoul, South Korea;2. Cancer Research Institute, Department of Tumor Biology, Seoul National University College of Medicine, , Seoul, South Korea;3. Department of Pathology, Seoul National University College of Medicine, , Seoul, South Korea;4. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, , Seoul, South Korea;5. Department of Nanobiomedical Science, Dankook University, , Cheonan, South Korea;6. Department of Pediatrics, College of Medicine, Yeungnam University, , Daegu, South Korea;7. Department of Pathology, Seoul National University Bundang Hospital, , Seongnam, South Korea;8. Ischemic/Hypoxic Disease Institute Medical Research Center, Seoul National University College of Medicine, , Seoul, South Korea |
| |
| 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. |
| |
| Keywords: | FOXO1 NF‐κ B gastric cancer cyclin D1 tissue microarrays |
|
|
