Expression And Significance Of PTEN, P-Akt And NF-κB Proteins In Middle Ear Cholesteatoma Epithelium

Background:Middle ear cholesteatoma is a epidermoid cyst characterized by an intrusion of keratinizing stratified squamous epithelium into the middle ear,resulting in the accumulation of keratinizing epithelium.Although cholesteatoma is not a malignancy,it is characterized by certain tumor-like features such as increased proliferation, atypical differentiation,chromosomal aberrations,and the destruction of surrounding tissues.The phosphatidylinositol 3-kinase-Akt/protein kinase B(PI3K-Akt /PKB) signaling transduction pathway is the most important pathway to protect epithelial cells against apoptosis,and it plays important roles in the signaling pathways in response to many growth factors and other extracellular stimuli to regulate cell survival.The activation of PI3K-Akt/ PKB signaling transduction pathway has been reported to protect epithelial cells against apoptosis and increase the proliferation of epithelial cells.The phosphatase and tensin homologue deleted on chromosome ten(PTEN) is known as a tumor suppressor gene to antagonize signaling through the PI3K-Akt/PKB pathway,thus it can regulate the PI3K-Akt/PKB pathway negatively.The transcription factor nuclear factor-κB(NF-κB) is one of downstream target factors of the PI3K-Akt/PKB pathway.As a multifunctional transcription factor,NF-κB participates in transcription regulation of many genes,and it is of core importance in the regulation of cell proliferation.The activation of PI3K-Akt/PKB signaling transduction pathway leads to cell survival through up-regulation of NF-κB.In this study,SP immunohistochemical method was used to detect expressions of PTEN,P-Akt and NF-κB proteins in cholesteatoma epithelium,and the relationships among the three proteins were analyzed. By this way,we explore the possible role of cell survival mechanism in middle ear cholesteatoma modulated by the PI3K-Akt/PKB pathway.Objective:To determine the expressions of PTEN,P-Akt and NF-κB proteins in middle ear cholesteatoma and their relationship, and explore their important roles in cellular survival mechanisms involved in cholesteatoma epithelial cells.Methods:SP immunohistochemical assay was used to detect expressions of PTEN,P-Akt and NF-κB proteins in 30 human middle ear cholesteatoma tissues and 15 normal skin specimens collected from the external ear canal.Results:The positive rate of PTEN protein expression in middle ear cholesteatoma epithelium was 36.7%(11/30),however,this rate in normal skin specimens collected from the extemal ear canal was 93.3%(14/15),and the former was significantly lower than the latter(P＜0.01).The positive rates of P-Akt protein expression in middle ear cholesteatoma epithelium and normal extemal ear canal skin were 70.0%(21/30) and 26.7%(4/15) respectively,and the difference between the two groups was statistically significant(P＜0.01).The positive expression rates of NF-κB protein in middle ear cholesteatoma epithelium and normal external ear canal skin were 63.3%(19/30) and 20.0%(3/15) respectively,and there was also a statistical significance between the two groups(P＜0.01).In 30 cases of human middle ear cholesteatoma epithelium,a negative correlation was found between the expression of PTEN and P-Akt or NF-κB proteins respectively (P＜0.01),and there was a highly positive correlation between P-Akt and NF-κB protein expression(P＜0.01).Conclusion:The abnormal expressions of PTEN,P-Akt and NF-κB proteins may have a close relationship with cholesteatoma epithelial hyperplasia.Loss of PTEN function increases the level of P-Akt,which can protect cholesteatoma epithelial cells against apoptosis and increase the proliferation of epithelial cells.