title: High-risk human papillomavirus type 16 E7 oncogene associates with Cdc25A over-expression in oral squamous cell carcinoma.
abstract: Cells expressing high-risk human papillomavirus (HPV) E7 protein display impaired checkpoint control after DNA damage and exhibit elevated rates of mutagenesis. Repression of HPV E7 expression results in the subsequent accumulation of hypophosphorylated retinoblastoma protein and repression of the Cdc25A genes. No study has been conducted to elucidate the role of Cdc25A in the development and progression of human oral carcinomas. To confirm Cdc25A protein expression together with HPV, immunohistochemistry, Western blotting, polymerase chain reaction (PCR), and reverse transcriptase (RT)-PCR were performed using various histological subtypes of oral carcinomas. Cdc25A protein was localized predominantly in the cell nuclei in carcinomas, and high expression was found in 54% of primary tumors. HPV-16 E7 was not found in non-neoplastic oral tissues, whereas it was observed in eight (36%) of 22 oral carcinomas. We found a significant correlation between Cdc25A over-expression and HPV-16 E7 positive carcinomas. There was a strong positive correlation between Cdc25A over-expression and tumor size and TNM stage. This study suggests that Cdc25A is likely to be an important mediator in the progression of oral tumors, and HPV-16 E7 may be a sensitive indicator of the involvement of viral oncogenes in oral carcinogenesis.
authors.affiliation: Department of Dental and Medical Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8553, Japan. bhawal2002@yahoo.co.in
authors.forename: Ujjal Kumar
authors.initials: UK
authors.lastname: Bhawal
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nomura
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sawajiri
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tsukinoki
authors.forename: Masa-Aki
authors.initials: MA
authors.lastname: Ikeda
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000737:chemistry / Q000473:pathology / Q000821:virology*; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk; D020687:cdc25 Phosphatases / Q000032:analysis*
chemical_list: D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; C059731:oncogene protein E7, Human papillomavirus type 16; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases