Survivin phosphorylation and M-phase promoting factor in oral carcinogenesis.
Survivin is a recently described inhibitor of apoptosis and mitotic regulator which is selectively over-expressed in human tumors. Its expression rate is predictive of disease progression, early recurrences and resistance to therapy. Up-regulation of survivin in oral pre-malignant lesions (OPL) and in oral squamous cell carcinoma (OSCC) has already been demonstrated in previous studies. A critical step for activation of survivin has been identified in the phosphorylation on Thr34 by the main mitotic kinase p34cdc2-cyclin B1. The aim of this work was to investigate the relationship between survivin, its phosphorylated active form (p-survivin) and M-phase promoting factor (MPF), p34cdc2-cyclin B1 in oral carcinogenesis. 32 OSCCs and 17 OPLs from surgical specimens were studied for cyclin B1, p-survivin, survivin, and p34cdc2 expression by immunohistochemistry. All cases of OSCC expressed survivin and its expression rate was correlated to p-survivin levels (P<0.05). Cyclin B1 was positive in 80% of cases, while p-34cdc2 was over-expressed in all OSCCs. All OPLs associated with OSCC expressed survivin and its levels were correlated to p-survivin levels (P<0.05). Cyclin B1 was positive in 70% of cases, while p-34cdc2 was positive in all OPLs. In conclusion, this study demonstrated that MPF, survivin and p-survivin are expressed during early and late phase of oral carcinogenesis. MPF proteins, which are co-expressed on mitotic apparatus, could represent a potential target for therapies based on manipulation of survivin phosphorylation, which would induce apoptosis in cancer cells.
Pannone
G
G
Department of Surgical Science, Section of Pathology, University of Foggia, Foggia, Italy.
Bufo
P
P
Serpico
R
R
Rubini
C
C
Zamparese
R
R
Corsi
F
F
Pedicillo
M C
MC
Pannone
G
G
Staibano
S
S
De Rosa
G
G
Lo Muzio
L
L
D014408:Biomarkers, Tumor / Q000378:metabolism*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D016200:Maturation-Promoting Factor / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D000077022:Survivin
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D016203:CDC2 Protein Kinase; D016200:Maturation-Promoting Factor