Survivin phosphorylation and M-phase promoting factor in oral carcinogenesis.

Abstract

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.

• Authors: G Pannone, P Bufo, R Serpico, C Rubini, R Zamparese, F Corsi, M C Pedicillo, G Pannone, S Staibano, G De Rosa, L Lo Muzio
• Journal: Histology and histopathology (Histol Histopathol) Vol. 22 Issue 11 Pg. 1241-9 (11 2007) ISSN: 1699-5848 [Electronic] Spain
• PMID: 17647197 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BIRC5 protein, human
• Biomarkers, Tumor
• CCNB1 protein, human
• Cyclin B
• Cyclin B1
• Inhibitor of Apoptosis Proteins
• Microtubule-Associated Proteins
• Neoplasm Proteins
• Survivin
• CDC2 Protein Kinase
• Maturation-Promoting Factor

Topics

• Biomarkers, Tumor (metabolism)
• CDC2 Protein Kinase (metabolism)
• Carcinoma, Squamous Cell (metabolism, pathology)
• Cyclin B (metabolism)
• Cyclin B1
• Female
• Humans
• Immunoenzyme Techniques
• Inhibitor of Apoptosis Proteins
• Male
• Maturation-Promoting Factor (metabolism)
• Microtubule-Associated Proteins (metabolism)
• Middle Aged
• Mouth Neoplasms (metabolism, pathology)
• Neoplasm Proteins (metabolism)
• Phosphorylation
• Precancerous Conditions (metabolism, pathology)
• Survivin