Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
Center of Excellence in Oral and Maxillofacial Biology, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
J Oral Pathol Med. 2018 Mar;47(3):260-267. doi: 10.1111/jop.12680. Epub 2018 Jan 30.
Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked β-N-acetylglucosamine (O-GlcNAc). However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC). Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading.
Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFR , and anti-phosphorylated-Akt antibodies following standard immunohistochemistry. The immunohistochemical (IHC) score was determined using the Fromowitz standard. Whole cell lysates of oral cancer cells and normal oral keratinocytes were immunoblotted with the anti-O-GlcNAc antibody.
The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFR and phosphorylated-Akt were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively). Similarly, expression of O-GlcNAcylated proteins in oral cancer cells and normal oral keratinocytes did not differ. In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFR and phosphorylated-Akt (P < .01 and P < .001, respectively). The IHC scores of O-GlcNAc or OGT were not determined to correlate with histological grading.
Unlike other types of cancers, our findings demonstrate that the levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in oral cancer cells and are not associated with the histological grading of OSCC.
在各种癌症中，常见的两种翻译后修饰机制是蛋白质磷酸化和 O-连接β-N-乙酰氨基葡萄糖（O-GlcNAc）糖基化。然而，在口腔鳞状细胞癌（OSCC）中仅报道了表皮生长因子受体（EGFR）/Akt 途径的磷酸化。因此，我们旨在确定与正常组织和口腔角质形成细胞相比，OSCC 组织和口腔癌细胞中的这两种翻译后修饰，并找到这些修饰与组织学分级的相关性。
用抗-O-GlcNAc、抗-O-GlcNAc 转移酶（OGT）、抗磷酸化-EGFR 和抗磷酸化-Akt 抗体对 32 例 OSCC 和 10 例正常福尔马林固定石蜡包埋切片进行免疫组织化学（IHC）检测。采用 Fromowitz 标准确定 IHC 评分。用抗-O-GlcNAc 抗体对口腔癌细胞和正常口腔角质形成细胞的全细胞裂解物进行免疫印迹。
OSCC 与正常组织之间 O-GlcNAc 或 OGT 的中位数 IHC 评分无差异，而 OSCC 中磷酸化-EGFR 和磷酸化-Akt 的 IHC 评分明显高于正常组织（P<.001 和 P<.01）。同样，口腔癌细胞和正常口腔角质形成细胞中 O-GlcNAc 化蛋白的表达没有差异。在 OSCC 组中，O-GlcNAc 和 OGT 的中位数 IHC 评分明显低于磷酸化-EGFR 和磷酸化-Akt（P<.01 和 P<.001）。O-GlcNAc 或 OGT 的 IHC 评分与组织学分级无关。
与其他类型的癌症不同，我们的研究结果表明，在 OSCC 组织或口腔癌细胞中，O-GlcNAcylation 的水平没有显著增加，并且与 OSCC 的组织学分级无关。
