“Eukaryotic initiation factor 4E phosphorylation status and 4E binding protein 1 expression in skin squamous cell carcinoma”


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Farhad Mashayekhi1, Zivar Salehi1
1Islamic Azad University, Tonekabon, Iran, Islamic Republic of

Background

Skin squamous cell carcinoma (SCC) is the second leading cause of death after melanoma. The dysregulation of protein synthesis may be a critical component in the process of malignant transformation. Increased protein synthesis is necessary for the translation of cells from quiescence to proliferation. Eukaryotic initiation factor 4E (eIF4E), an important regulator of translation, plays critical roles in cancer progression. eIF4E function is regulated partly by changes in its phosphoryaltion state. In addition, members of family of protein termed eIF4E-binding proteins (4E-BPs) bind to eIF4E and the formation of the eIF4F complex. The 4E-BPs strongly interact with eIF4E when in their phosphorylated state and dissociate from eIF4E upon hyperphosphorylation. The aim of this study was to determine the eukaryotic initiation factor 4E phosphorylation status and 4E-BP1 expression in SCC.?

Method

The total number of 112 skin samples (19 stage 0, 17 stage I, 16 stage II, 18 stage III, 20 stage IV SCCs and 22 normal tissues) were studied in this study. eIF4E and 4E-BP1 levels were determined by using western blot analysis and cap affinity choromatography using m7GTP- sepharose.

Results

The eIF4E expression levels in SCC samples significantly increased as compared to normal samples. A high expression of eIF4E and phosphorylated form of eIF4E are correlated with the advanced stage. Moreover, the expression of 4E-BP1 in SCC samples was significantly decreased as compared to control group.

Conclusion

It is concluded that a higher expression of eIF4E was correlated with advanced stages. The inverse relationship found between the increases in 4E-BP1 levels observed in skin cancer involvement would support the hypothesis that overexpression of eIF4E can be involved in tumorogenesis and a possible role of 4E-BP1 as a prognostic factor in the skin cancer.