title: Downregulation and translocation of nuclear ING4 is correlated with tumorigenesis and progression of head and neck squamous cell carcinoma.
abstract: ING4 (inhibitor of growth gene 4) is a new member of the ING gene family and is implicated in chromatin remodeling and repression of cell growth. In order to explore the roles of ING4 in head and neck squamous cell carcinoma (HNSCC), ING4 expression was assessed in 214 cases of HNSCC by immunohistochemistry using tissue microarray, and in three oral SCC cell lines by immunohistochemistry and Western blotting. Expression of ING4 was also compared to clinicopathological variables, TUNEL assay staining, and the expression of several tumorigenic markers. We found nuclear expression of ING4 was gradually decreased from non-cancerous epithelium and dysplasia to HNSCC and was negatively correlated with a poorly-differentiated status, T staging, and TNM staging in HNSCC. In contrast, cytoplasmic expression of ING4 was significantly increased in HNSCC and was significantly associated with lymph node metastasis and 14-3-3η expression. In addition, nuclear expression of ING4 was positively correlated with p21 and p300 expression and with the apoptotic index. These results suggest that the decreases in nuclear ING4 may play important roles in tumorigenesis, progression and tumor differentiation in HNSCC. Increases in cytoplasmic ING4 may be due to 14-3-3η binding and may also be involved in malignant progression. Nuclear ING4 may modulate the transactivation of target genes, promoting apoptosis and cell cycle arrest through interactions with p300 and p21.
authors.affiliation: Kanagawa Cancer Center Research Institute, 1-1-2 Nakao, Asahi-ku, Yokohama 241-0815, Japan.
authors.forename: Xiao-han
authors.initials: XH
authors.lastname: Li
authors.forename: Keiji
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Yang
authors.initials: Y
authors.lastname: Zheng
authors.forename: Akira
authors.initials: A
authors.lastname: Noguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishida
authors.forename: Shinji
authors.initials: S
authors.lastname: Masuda
authors.forename: Xiang-hong
authors.initials: XH
authors.lastname: Yang
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D007564:Japan; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018398:Homeodomain Proteins; C483230:ING4 protein, human; D025521:Tumor Suppressor Proteins; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human