Pei-Hsien Liao1, Yen-Yun Wang2, Wen-Chen Wang3, Chung-Ho Chen4, Yu-Hsun Kao4, Jing-Wei Hsu4, Ching-Yi Chen5, Ping-Ho Chen1, Shyng-Shiou Yuan6, Yuk-Kwan Chen7. 1. School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 2. 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. 3. School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Oral Pathology & Maxillofacial Radiology, Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Oral & Maxillofacial Imaging Center, Kaohsiung Medical University, Kaohsiung, Taiwan. 4. Division of Oral & Maxillofacial Surgery, Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 5. Division of Oral Pathology & Maxillofacial Radiology, Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Oral & Maxillofacial Imaging Center, Kaohsiung Medical University, Kaohsiung, Taiwan. 6. Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Obstetrics and Gynecology and Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: yuanssf@ms33.hinet.net. 7. School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Oral Pathology & Maxillofacial Radiology, Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Oral & Maxillofacial Imaging Center, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: k0285@ms22.hinet.net.
Abstract
OBJECTIVE: This study investigated SPRY2 expression in human oral potentially malignant disorders (OPMDs) and oral squamous cell carcinomas (OSCCs). METHODS: 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. RESULTS: 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. CONCLUSIONS: Our results indicated that SPRY2 overexpression is associated with human oral squamous-cell carcinogenesis.
OBJECTIVE: This study investigated SPRY2 expression in human oral potentially malignant disorders (OPMDs) and oral squamous cell carcinomas (OSCCs). METHODS: 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 humanoral 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 BRAFV600E point mutation assays. RESULTS: 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 BRAFV600E 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. CONCLUSIONS: Our results indicated that SPRY2 overexpression is associated with human oral squamous-cell carcinogenesis.