title: Homeobox C5 expression is associated with the progression of 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis.
abstract: BACKGROUND
  Aberrant expression of homeobox genes (HOX), normally required for the differentiation of a particular tissue, has been reported in several types of cancer, but poorly addressed in oral squamous cell carcinoma (OSCC). The present study investigated the expression of HOXC5 in OSCC and identified molecular biomarker whose expression is associated with the multistep oral carcinogenesis.
  
  
  METHODS
  The expression of HOXC5, proliferation cell nuclear antigen (PCNA), and Bcl-2 was examined by RT-PCR and Western blot analysis and confirmed by immunohistochemistry and transferase-mediated dUTP nick end-labeling (TUNEL) assay in a 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis model.
  
  
  RESULTS
  Homeobox genes C5 was overexpressed in SCC tissues, but not in normal tissues by RT-PCR and Western blot analysis. Along with the progress of multistep carcinogenesis, the levels of HOXC5 expression of mRNA and protein significantly increased during the dysplasia (moderate to severe dysplasia) when compared with normal and hyperplasia. The levels of PCNA and Bcl-2 were sequentially increased from hyperplasia to dysplasia and SCC. By immunohistochemistry, HOXC5 expression was significantly increased in dysplasia, whereas PCNA expression was gradually increased during tongue carcinogenesis. TUNEL-positive cells were increased until dysplasia, but reduced in SCC.
  
  
  CONCLUSIONS
  These results indicate that overexpression of HOXC5 is correlated with oral carcinogenesis and strongly contributed to the development of OSCC. HOXC5 may be a useful biomarker and has an emerging therapeutic target of OSCC.
authors.affiliation: Department of Pathology and Research Center for Oral Disease Regulation of Aged, School of Dentistry, Chosun University, Gwangju, Korea.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Moon
authors.forename: Mee-Young
authors.initials: MY
authors.lastname: Ahn
authors.forename: Seong-Min
authors.initials: SM
authors.lastname: Kwon
authors.forename: Soo-A
authors.initials: SA
authors.lastname: Kim
authors.forename: Sang-Gun
authors.initials: SG
authors.lastname: Ahn
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Yoon
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000009:adverse effects*; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000235:genetics; D045744:Cell Line, Tumor; D003043:Cocarcinogenesis; D004195:Disease Models, Animal; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005801:Genes, Homeobox / Q000235:genetics; D018398:Homeodomain Proteins / Q000032:analysis* / Q000235:genetics; D006801:Humans; D006965:Hyperplasia; D007972:Leukoplakia, Oral / Q000139:chemically induced / Q000235:genetics; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014059:Tongue / Q000473:pathology; D014062:Tongue Neoplasms / Q000139:chemically induced* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; D018398:Homeodomain Proteins; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D015112:4-Nitroquinoline-1-oxide