Expression of cell cycle control proteins in normal epithelium, premalignant and malignant lesions of oral cavity.
In this study, we examined the expression of cyclins, cyclin dependent kinase (CDKs) and CDK inhibitors by immunohistochemical analysis in 20 normal mucosa, 42 epithelial dysplasia (ED), and 117 oral squamous cell carcinoma. Neither Cyclin D1 nor CDK2 were detectable in normal tissue and ED. Their presence, however, was detectable in squamous cell carcinoma (SCCs) (Cyclin D1, 35.9%; CDK2, 66.7%). Cyclin E was detectable in 57.1% of severe ED and 62.8% of SCCs. For the CDK inhibitors, these proteins were detectable in all normal mucosa and most of the mild and moderate ED. For severe ED, expression of these proteins was not observed in some cases (p12(DOC-1), 14.3%; p16(INK4A), 28.6%; p27(KIP1), 7.1%). For SCCs, the expression of p12(DOC-1) was lost in 71.8%, p16(INK4A) in 69.2% and p27(KIP1) in 35.9%. These results suggest that elevated expression of cyclin D1, cyclin E, CDK2 and loss of p12(DOC-1), p16(INK4A) and p27(KIP1) may contribute to the multistep nature of oral carcinogenesis.
Shintani
Satoru
S
Department of Oral and Maxillofacial Surgery, Ehime University School of Medicine, Ehime, Japan. satoru@m.ehime-u.ac.jp
Mihara
Mariko
M
Nakahara
Yuji
Y
Kiyota
Akihisa
A
Ueyama
Yoshiya
Y
Matsumura
Tomohiro
T
Wong
David T W
DT
D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases; D002294:Carcinoma, Squamous Cell / Q000737:chemistry*; D002352:Carrier Proteins / Q000032:analysis; D018797:Cell Cycle Proteins / Q000032:analysis*; D019938:Cyclin D1 / Q000032:analysis; D019927:Cyclin E / Q000032:analysis; D051357:Cyclin-Dependent Kinase 2; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000032:analysis; D004848:Epithelium / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D009061:Mouth Mucosa / Q000737:chemistry*; D009062:Mouth Neoplasms / Q000737:chemistry*; D011230:Precancerous Conditions / Q000737:chemistry*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis
D014408:Biomarkers, Tumor; C096151:CDK2AP1 protein, human; C436291:CDKN1B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019927:Cyclin E; D019941:Cyclin-Dependent Kinase Inhibitor p16; D047908:Intracellular Signaling Peptides and Proteins; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases