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Abstract
O-linked β-N-acetylglucosamine modification is an important post-translational modification, emerging as a novel regulatory mechanism in various cellular events. Recently, several studies have shown that O-GlcNAcylation plays an essential role in human breast, lung, and colon cancers. With regard to skin cancers, the role of O-GlcNAcylation has yet to be elucidated. To investigate whether O-GlcNAcylation is linked to human skin tumor development, immunohistochemical analysis was performed to investigate the presence of O-GlcNAcylation in various skin tumors. We evaluated the levels of O-GlcNAcylation, O-GlcNAc transferase, and O-GlcNAcase in 29 benign tumors, 12 premalignant tumors, and 26 malignant tumors in skin. Compared to the benign tumors, premalignant and malignant tumors had increased patterns of O-GlcNAcylation. In addition, the O-GlcNAc transferase and O-GlcNAcase levels were higher in premalignant and malignant tumors than in benign tumors. Interestingly, O-GlcNAcase levels were significantly increased in premalignant tumors compared to benign and malignant tumors. These results suggest that O-GlcNAcylation of proteins may play an important role in the development of human skin tumors.
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Fig. 1.
The O-GlcNAcylation cycle. O-GlcNAcylation is catalyzed by the enzyme O-GlcNAc transferase(OGT), which transfers GlcNAc from UDP-GlcNAc to the target protein. Conversely, O-GlcNAc is removed from the protein by O-GlcNAcase(OGA).
Fig. 2.
Immunohistochemical analysis of O-GlcNAcylation in the epidermis. Normal skin tissues were incubated with anti-O-GlcNAc antibody (RL2), anti-O-GlcNAc transferase (OGT) antibody, and anti-O-GlcNAcase (OGA) antibody. RL2-positive staining is slightly decreased in the upper layer. OGT is observed in all layers, and intense OGA staining is seen in the upper layer(200×).
Fig. 3.
Immunohistochemical analysis of O-GlcNAcylation in skin tumors. Skin tumors were categorized as benign, premalignant, or malignant and stained with(A) anti-O-GlcNAc antibody(RL2)(B) anti-O-GlcNAc transferase(OGT) antibody, and(C) anti-O-GlcNAcase (OGA) antibody. The upper panel represents a benign tumor (neurofibroma), the middle panel represents a premalignant tumor (actinic triplicate and data are expressed as the mean±standard deviation(p⁄0.05). keratosis), and the lower panel represents a malignant tumor (squamous cell carcinoma) (200×). Measurements were conducted in triplicate and data are expressed as the mean±standard deviation (p<0.05).
Table 1.
Summary of immunohistochemistry analysis
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