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Forkhead transcription factor FOXO 1 inhibits nuclear factor‐κB in gastric cancer
Author(s) -
Yu DaAe,
Yoon Jiyeon,
Ko Young San,
Park Jinju,
Kim Sue Youn,
Kim Min A,
Kim Ji Hun,
Jung Jieun,
Cheon Younghee,
Lee Hye Seung,
Kim Woo Ho,
Lee Byung Lan
Publication year - 2014
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/apm.12247
Subject(s) - transcription factor , foxo1 , cyclin d1 , cancer , cancer research , biology , immunohistochemistry , cancer cell , microbiology and biotechnology , cell cycle , gene , immunology , genetics
FOXO 1, 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 FOXO 1 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 p FOXO 1, the inactive form of FOXO 1, was positively correlated with nuclear RelA expression (p = 0.024). In addition, the expressions of p FOXO 1 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 FOXO 1 overexpression by transfection of FOXO 1 AAA mutant gene suppressed NF ‐κB activation in SNU ‐484 gastric cancer cells. These results suggest that FOXO 1 and NF ‐κB are negatively associated and that FOXO 1 is a negative upstream regulator of NF ‐κB in gastric cancer.