Fas antigen and Fas ligand with signaling pathway in Squamous carcinoma cells

鳞状癌细胞中Fas抗原和Fas配体与信号通路的关系

• 批准号: 12671958
• 负责人: FUKUDA Junichi
• 金额: $ 2.11万
• 依托单位: Kyushu Dental College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671958/
• 关键词: Fas ligand; Fas antigen; apoptosis; oral cancer; Fasリガンド

To determine the relationship between the expression of Fas antigen and apoptosis in oral epithelium, we investigated the expression of Fas antigen in oral mucosa by immunohistochemical and immunoblotting methods. Fas antigen distributed in stratum spinosum and basal part of the stratum coreneum in normal human gingiva. Expression of Fas antigen was related to the degree of the tumor differentiation. Using RT-PCR method, mRNA for Fas antigen was detected in the human oral squamous cell carcinoma cell line SCC-25. In serum-free medium, a monoclonal anti-Fas antibody stimulated the expression of Fas antigen in SCC-25 cells. Fas antigen was localized in the cytoplasm and at the cell membrane.Protein phosphatase inhibitors, okadaic acid and calyculin A induced apoptosis in SCC-25 cells and another human squamous carcinoma cells lines SCC KN and SCC TF cells. Okadaic acid also simulated the expression of mRNA and protein of Fas antigen and Fas ligand in SCC-25 cells in time- and dose-dependent manners. Using immunoblotting and electrophoretic mobility shift assays, okadaic acid activated NF-κB, transcriptional factor, in SCC-25 cells. Our results indicate that okadaic acid mediate apoptosis by inducing of NF-κB activity that may stimulate the transcriptional activity of Fas ligand in SCC-25 cells.

为探讨口腔粘膜Fas抗原表达与细胞凋亡的关系，我们采用免疫组化和免疫印迹方法检测了口腔粘膜Fas抗原的表达。正常人牙龈中Fas抗原分布于棘层和角质层基底部。Fas抗原表达与肿瘤分化程度有关。应用RT-PCR方法检测人口腔鳞癌细胞株SCC-25中Fas抗原mRNA的表达。在无血清培养条件下，抗Fas单克隆抗体可刺激SCC-25细胞Fas抗原的表达。蛋白磷酸酶抑制剂冈田酸和calyculin A可诱导SCC-25细胞和另一株人鳞状细胞癌细胞系SCC KN和SCC TF细胞凋亡。冈田酸对SCC-25细胞Fas抗原和Fas配体的mRNA和蛋白表达也有时间和剂量依赖性的促进作用。应用免疫印迹和电泳迁移率变动分析，冈田酸激活了SCC-25细胞中的NF-κB（转录因子）。我们的结果表明冈田酸通过诱导NF-κB活性而介导SCC-25细胞凋亡，NF-κB活性可能刺激Fas配体的转录活性。

项目成果

Yasuhiro Morimoto: "Upregulation of the expression of Fas antigen and Fas ligand in a human submandibular gland ductal cell line by okadaic acid."Archives of Oral Biology. 45・8. 657-666 (2000)

Yasuhiro Morimoto：“冈田酸上调人颌下腺导管细胞系中 Fas 抗原和 Fas 配体的表达。”口腔生物学档案 45・8 (2000)。

Yukoh Muraki: "Fas antigen expression and outcome of squamous cell carcinoma."International of Oral and Maxillofacial Surgery. 29・5. 360-365 (2000)

Yukoh Muraki：“鳞状细胞癌的 Fas 抗原表达和结果”。国际口腔颌面外科杂志 29・5（2000 年）。

Kaho Goto: "Okadaic acid stimulates apoptosis through expression of Fas receptor and Fas ligand in human squamous carcinoma cells"Oral Oncology. 38. 16-22 (2002)

Kaho Goto：“冈田酸通过人鳞状癌细胞中 Fas 受体和 Fas 配体的表达刺激细胞凋亡”口腔肿瘤学。

Hirohiko Okamura: "Peplomycin-induced apoptosis in oral squamous carcinoma cells depend on bleomycin sensitivity."European Journal of Cancer Part B,Oral Oncology. (In press).

Hirohiko Okamura：“佩普霉素诱导的口腔鳞状癌细胞凋亡取决于博莱霉素敏感性。”欧洲癌症杂志 B 部分，口腔肿瘤学。

Yasuhiro Morimoto: "Alteration of argyrophilic nucleolar organizer region associated (Ag-NOR) proteins in apoptosis-induced human salivary gland cells and human squamous carcinoma cells"Journal of Oral Pathology and Medicine. 30. 193-199 (2001)

Yasuhiro Morimoto：“凋亡诱导的人唾液腺细胞和人鳞状癌细胞中嗜银核仁形成区相关 (Ag-NOR) 蛋白的改变”口腔病理学与医学杂志。