Localization Research Of 14-3-3 Proteins And Its Significance In Human Astrocyte Tumors

Astrocyte tumors are the most frequent brain tumors and are among the most aggressive of all human malignancies. It accounts for about 50%~60% of human brain tumor in adults. Even with best conventional therapy, the prognosis is dismal. The mean survival time after surgical intervention is within one year in glioblastoma multiformes which is the most malignany in astrocytoma. Astrocyte tumors development occurs by means of a series of dynamic changes in the genome that confer growth advantages to transformed cells. Among them, suppression of apoptosis is a common phenomenon. By extending the lifespan of abnormal cells, accumulation of transforming mutations can occur, thereby promoting development of the malignant phenotype and resistance to conventional cytotixic agents. Therefore, futher understanding the mechanism of how astrocytoma cells evading apoptosis is crucial for designing new ways restoration of apoptotic pathways in astrocytomas.The term14-3-3 refers to family fo highly conserved, small, acidic dimeric proteins of 28-33 kDa. They received their name in 1967 during a systematic classification of brain proteins that was based on their fraction number on anion-exchange chromatography and migration position in gel electrophoresis. Proteins of this family have been found in all eukaryotic organisms studied so far. However, the highest tissue concertration of 14-3-3 proteins is found in the brain,comprising about 1% of its total soluble protein. There are seven known mammalian 14-3-3 proteins encoded by separate genes. Up to now, over 200 14-3-3-binding ligands are identified, and the number of 14-3-3 binding partners is still increasing. Considering the number of binding partners, it is not surprising that 14-3-3 proteins play crucial roles in regulating multiple cellular processes-they include the maintenance of cell cycle checkpoints and DNA repair, the prevention of aoptosis, the onset of cell differentiation and senescence, and the coordination of cell adhesion and motility. In addition to their important roles in many mormal physiology processes, 14-3-3 proteins have attracted much recent interest in the etiopathogenesis of human cancers owing to their involvement in the prevention of apoptosis. At present, there is no research concerning the expression and role of 14-3-3 isoforms in astrocytoma. In this study, we addressed this issue from the following aspect.The expression and its significance of 14-3-3 isoforms in astrocyte tumors: The expression of 14-3-3 isoforms was detected in 80 cases of formalin-fixed, paraffin embedded archival tumor tissue from patients with astrocyte tumors, and 10 normal human brain tissues by immunohistochemical ABC method. The results showed that, in the normal control brains, 14-3-3 isoforms immunoreactivity was localized mainly in the neuronal somata and processes, while only weak expression ofε,ζandθwas found in some glial cells. Howeverβ,ε,ζ,ηandθisoforms'immunoreactivity was seen in the majority of astrocyte tumor samples and its immunoreactivity score was increased markedly with an increase in the pathologic grade of human astrocyte tumors. These results indicate that the five isoforms ,especiallyβandηisoforms,may play an important role in tumorigenesis of human astrocyte tumors.In summary, in the first time, this research suggested thatβandηisoforms may be key proteins in initiation and progress of human astrocyte tumors, its mechanism may involve the anti-apoptotic effect of 14-3-3 isoforms in the tumorogenesis and development of astrocyte tumors. 14-3-3 isoforms may be considered as a potential and promising target for gene therapy of astrocyte tumors.