title: 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.
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Da-Ae
authors.initials: DA
authors.lastname: Yu
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Yoon
authors.forename: Young San
authors.initials: YS
authors.lastname: Ko
authors.forename: Jinju
authors.initials: J
authors.lastname: Park
authors.forename: Sue Youn
authors.initials: SY
authors.lastname: Kim
authors.forename: Min A
authors.initials: MA
authors.lastname: Kim
authors.forename: Ji Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Jieun
authors.initials: J
authors.lastname: Jung
authors.forename: Younghee
authors.initials: Y
authors.lastname: Cheon
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Byung Lan
authors.initials: BL
authors.lastname: Lee
mesh_terms: D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000096:biosynthesis; D019927:Cyclin E / Q000096:biosynthesis; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D009154:Mutation; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000473:pathology*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D019927:Cyclin E; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D019394:Ki-67 Antigen; C498143:RELA protein, human; D016160:Retinoblastoma Protein; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1
keywords: FOXO1; NF-κB; cyclin D1; gastric cancer; tissue microarrays