School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Arch Oral Biol. 2018 Mar;87:131-142. doi: 10.1016/j.archoralbio.2017.12.021. Epub 2017 Dec 27.
This study investigated SPRY2 expression in human oral potentially malignant disorders (OPMDs) and oral squamous cell carcinomas (OSCCs).
75 OSCCs, 23 OPMDs with malignant transformation (MT), 17 OPMDs without MT, and eight normal oral mucosa (NOM) tissues were used for immunohistochemical staining; three OSCC tissues with normal tissue counterparts were used for western blotting. Three human oral cancer cell lines (OCCLs), an oral precancer cell line (DOK), and a NOM primary culture (NOMPC) were used for western blotting; OCCLs and NOMPC were employed for real-time quantitative reverse transcription-polymerase chain reaction. OCCLs were evaluated in terms of proliferation, migration, invasion and BRAF V600E point mutation assays.
Significantly increased SPRY2 protein expression was observed in OSCCs as compared with NOM, and SPRY2 expression also differed between OSCC patients with and without lymph-node metastasis. SPRY2 protein and mRNA expressions were significantly enhanced as compared with NOMPC. Increased phospho-ERK expression was observed in OCCLs as compared with NOMPC. Significant decreases in the proliferation rate, degrees of migration and invasion were noted in OCCLs with SPRY2 siRNA transfection as compared with those without SPRY2 siRNA transfection. No BRAF V600E point mutation was observed for OCCLs as compared with NOMPC. A significantly increased SPRY2 protein level was noted in OPMDs with MT as compared to those without MT, and was also found in OPMDs with MT in comparison with NOM, as well as in DOK in comparison with NOMPC.
Our results indicated that SPRY2 overexpression is associated with human oral squamous-cell carcinogenesis.
本研究调查了 SPRY2 在人口腔潜在恶性疾病（OPMDs）和口腔鳞状细胞癌（OSCCs）中的表达。
使用免疫组织化学染色法检测 75 例 OSCCs、23 例有恶性转化（MT）的 OPMDs、17 例无 MT 的 OPMDs 和 8 例正常口腔黏膜（NOM）组织；3 例 OSCC 组织与正常组织对照进行 Western blot 检测。使用 Western blot 检测 3 个人口腔癌细胞系（OCCLs）、一个口腔癌前细胞系（DOK）和一个 NOM 原代培养物（NOMPC）；OCCLs 和 NOMPC 用于实时定量逆转录聚合酶链反应。对 OCCLs 进行增殖、迁移、侵袭和 BRAF V600E 点突变检测。
与 NOM 相比，OSCCs 中 SPRY2 蛋白表达明显增加，且 OSCC 患者中存在淋巴结转移的患者与无淋巴结转移的患者之间的 SPRY2 表达也存在差异。与 NOMPC 相比，SPRY2 蛋白和 mRNA 表达均显著增强。与 NOMPC 相比，OCCLs 中磷酸化 ERK 表达增加。与未转染 SPRY2 siRNA 的 OCCLs 相比，转染 SPRY2 siRNA 的 OCCLs 的增殖率、迁移和侵袭程度显著降低。与 NOMPC 相比，OCCLs 中未观察到 BRAF V600E 点突变。与无 MT 的 OPMDs 相比，MT 的 OPMDs 的 SPRY2 蛋白水平明显升高，与无 MT 的 OPMDs 相比，与 NOM 相比，与 NOMPC 相比，DOK 也升高。
我们的研究结果表明，SPRY2 过表达与人类口腔鳞状细胞癌的发生有关。
