title: Decreased nuclear expression and increased cytoplasmic expression of ING5 may be linked to tumorigenesis and progression in human head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  This study aimed to assess the protein level of inhibitor of growth gene 5 (ING5) in head and neck squamous cell carcinoma (HNSCC) and to explore its roles in tumorigenesis and cancer progression.
  
  
  METHODS
  ING5 expression was assessed in 172 cases of HNSCC by immunohistochemistry using tissue microarray, and in 3 oral SCC cell lines by immunohistochemistry and Western blot. Expression of ING5 was compared with clinicopathological variables, TUNEL assay staining, and the expression of several tumorigenic markers. In addition, double immunofluorescence labeling was performed in order to analyze the colocalization of ING5 with p300 and p21.
  
  
  RESULTS
  ING5 expression was primarily observed in the nuclei, but was also occasionally found in the cytoplasm of both SCC cell lines and tissue samples of HNSCC. Nuclear expression of ING5 in HNSCC was significantly lower than that of non-cancerous epithelium, and was positively correlated with a well-differentiated status. In contrast, cytoplasmic expression of ING5 was significantly increased in HNSCC, and was inversely correlated with a well-differentiated status and nuclear ING5 expression. In addition, nuclear expression of ING5 was positively correlated with p21 and p300 expression, and with the apoptotic index. In contrast, cytoplasmic expression of ING5 was negatively correlated with the expression of p300, p21, and PCNA. Although no statistical association was found between the expression of nuclear ING5 and mutant p53 in HNSCC, patients with high expression of nuclear ING5 tended to have converse prognoses when grouped according to mutant p53 expression.
  
  
  CONCLUSIONS
  Our results suggest that a decrease in nuclear ING5 localization and cytoplasmic translocation are involved in tumorigenesis and tumor differentiation in HNSCC. Nuclear ING5 may modulate the transactivation of target genes, and may promote apoptosis and cell cycle arrest by interacting with the p300 and p21 proteins. ING5 may function as a tumor suppressor gene or oncogene tightly linked with p53 status, and may play an important role in the prognosis of HNSCC patients. Therefore, we propose that ING5 represents a novel potential molecular therapeutic target for HNSCC.
authors.affiliation: Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Li
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishida
authors.forename: Akira
authors.initials: A
authors.lastname: Noguchi
authors.forename: Yang
authors.initials: Y
authors.lastname: Zheng
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Xianghong
authors.initials: X
authors.lastname: Yang
authors.forename: Shinji
authors.initials: S
authors.lastname: Masuda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D003593:Cytoplasm / Q000737:chemistry*; D018450:Disease Progression; D050881:E1A-Associated p300 Protein / Q000032:analysis; D005260:Female; D005455:Fluorescent Antibody Technique; D006258:Head and Neck Neoplasms / Q000737:chemistry / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014157:Transcription Factors / Q000032:analysis / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000502:physiology*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C508131:ING5 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human