Department of Oral and Maxillofacial Surgery, Oral Restitution, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Odontology. 2012 Jul;100(2):156-63. doi: 10.1007/s10266-011-0033-2. Epub 2011 May 24.
Overexpression of epidermal growth factor receptor (EGFR) is associated with resistance to chemotherapy and radiotherapy, advanced tumor stage, invasion, metastasis and poor prognosis in malignant tumors. EGFR, therefore, has been an attractive molecular target for chemotherapy. However, the results of clinical studies using inhibitors of its kinase activity have not been promising because the response rates were at most 20%. Sodium-glucose co-transporter 1 (SGLT1) is a membrane protein that mediates the transport of glucose across cellular membranes. EGFR physically associates with and stabilizes SGLT1 to promote glucose uptake into cancer cells through a kinase-independent process. The purpose of this study was to investigate the coexpression of SGLT1 and EGFR and its relationships with clinicopathological features in oral squamous cell carcinoma (OSCC). SGLT1 and EGFR were detected in all OSCC cell lines, and the expression levels of SGLT1 were significantly correlated with those of EGFR. Pearson product-moment correlation coefficient of SGLT1 and EGFR was 0.89 (P = 0.016). The immunohistochemical study using the surgical specimens in 52 patients with tongue SCC also showed a significant correlation between SGLT1 and EGFR. Moreover, SGLT1/EGFR expression was inversely related to tumor differentiation among the 5 clinicopathological factors (P = 0.004). SGLT1/EGFR coexpression might be required in the de-differentiation of OSCC, but further study is needed to clarify the implication of these proteins in the manifestation of malignancy and clinical significance.
表皮生长因子受体（EGFR）的过表达与化疗和放疗耐药、肿瘤晚期、侵袭、转移和恶性肿瘤预后不良有关。因此，EGFR 一直是化疗的一个有吸引力的分子靶点。然而，使用其激酶活性抑制剂的临床研究结果并不理想，因为反应率最高只有 20%。钠-葡萄糖共转运蛋白 1（SGLT1）是一种膜蛋白，可介导葡萄糖穿过细胞膜的运输。EGFR 与 SGLT1 物理结合并稳定 SGLT1，通过一种非激酶依赖的过程促进葡萄糖进入癌细胞的摄取。本研究旨在探讨 SGLT1 和 EGFR 的共表达及其与口腔鳞状细胞癌（OSCC）临床病理特征的关系。在所有 OSCC 细胞系中均检测到 SGLT1 和 EGFR，SGLT1 的表达水平与 EGFR 的表达水平显著相关。SGLT1 和 EGFR 的 Pearson 积矩相关系数为 0.89（P = 0.016）。对 52 例舌 SCC 患者手术标本的免疫组织化学研究也表明 SGLT1 与 EGFR 之间存在显著相关性。此外，SGLT1/EGFR 表达与 5 个临床病理因素中的肿瘤分化呈负相关（P = 0.004）。SGLT1/EGFR 共表达可能是 OSCC 去分化所必需的，但需要进一步研究来阐明这些蛋白在恶性表型和临床意义中的作用。
