title: Skp2 and Jab1 expression are associated with inverse expression of p27(KIP1) and poor prognosis in oral squamous cell carcinomas.
abstract: Previous studies have shown that low levels of p27(KIP1), an inhibitor of G1 cyclin-dependent kinases (CDK), are associated with high aggressiveness and poor prognosis in a variety of cancers. Decreased levels of p27(KIP1) are caused, at least in part, by an acceleration of degradation with Skp2 (S-phase kinase-associated protein 2) and Jab1 (Jun activation domain-binding protein 1). This investigation was undertaken to examine whether the Skp2 and Jab1 expression is correlated with p27(KIP1) protein levels, and how it is clinically relevant in oral squamous cell carcinoma (OSCC). The correlations between p27(KIP1) and Skp2, and p27(KIP1) and Jab1 expression were evaluated by Western blot analysis. Immunohistochemical analysis was done in 75 cases of OSCC. A strongly significant inverse correlation was found between levels of p27(KIP1) and Skp2, and p27(KIP1) and Jab1 (p < 0.0001). Thus, decreased levels of p27(KIP1) were associated with strongly increased levels of Skp2 and Jab1, whereas high levels of p27(KIP1) coincided with low levels of Skp2 and Jab1. Reductions of p27(KIP1) expression and overexpression of Skp2 and Jab1 were significantly associated with cervical lymph node metastasis and poor prognosis. Overexpression of Skp2 and Jab1 is associated with the reduction of p27(KIP1) expression, and may have a role in the progression of OSCC.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ehime University School of Medicine, Shigenobu-cho, Ehime, Japan. satoru@m.ehime-u.ac.jp
authors.forename: Satoru
authors.initials: S
authors.lastname: Shintani
authors.forename: Chunnun
authors.initials: C
authors.lastname: Li
authors.forename: Mariko
authors.initials: M
authors.lastname: Mihara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hino
authors.forename: Koh-Ichi
authors.initials: K
authors.lastname: Nakashiro
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hamakawa
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D000075686:COP9 Signalosome Complex; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology*; D045744:Cell Line, Tumor; D046508:Culture Techniques; D004268:DNA-Binding Proteins / Q000032:analysis*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins / Q000032:analysis*; D009062:Mouth Neoplasms / Q000737:chemistry* / Q000473:pathology*; D009124:Muscle Proteins; D010447:Peptide Hydrolases; D011237:Predictive Value of Tests; D011379:Prognosis; D044786:S-Phase Kinase-Associated Proteins / Q000032:analysis*; D016019:Survival Analysis; D014157:Transcription Factors / Q000032:analysis*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D044786:S-Phase Kinase-Associated Proteins; C058992:Tagln protein, mouse; D014157:Transcription Factors; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; C501490:Cops5 protein, mouse; D000075686:COP9 Signalosome Complex