Analysis of abnormal DNA structure and down regulation of a new tumor suppressor, FEZ1 gene, in oral squamous cell carcinoma.

口腔鳞状细胞癌中异常 DNA 结构和新型抑癌基因 FEZ1 基因的下调分析。

• 批准号: 12671925
• 负责人: YAMA Mitsuru
• 金额: $ 2.11万
• 依托单位: Tokyo Dental College (2002)Chiba University (2000-2001)
• 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 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671925/
• 关键词: Chromosome 8p22; FEZ1 gene; tumor suppressor gene; oral cancer; methvlation; down-reeulation; demethvaktion; 5-aza-2'-deoxvcvtidine; 5-aza-2'deoxycytidine; 口腔扁平上皮癌; 発現減弱・消失; 第8番染色体

Allelic deletions on the short arm of chromosome 8 (8p) are frequent events inseveral human malignancies, including oral cancer. We have examined and found two common regions of deletion on 8p (8pl2, 8p22) in oral squamous cell carcinomas (SCC) s. The possible involvement of FEZl/LZTSl (FEZ1) gene, a candidate tumor suppressor gene, mapped at 8p22, was also evaluated. Here we analyzed whether FEZl alterations play arole in the development and progression of oral SCCs. In present study, we examined FEZ1 expression in 31 primary oral SCCs and 8 SCC-derived cell line by reverse transcription-PCR (RT-PCR). Thirty-five % of tumor (ll of 31) and 100% of cell lines (8 of 8) showed absent or reduced mRNA gene expression. Furthermore, to investigate the mechanism for silencing, cell were cultured with 5-aza-2'-deoxycytidine and all of cell linesshowed restoration by demethylating agent. These findings suggest that inactivation of the FEZ1 gene may contribute to the development of oral SCCs.

8 号染色体短臂 (8p) 上的等位基因缺失是多种人类恶性肿瘤（包括口腔癌）中的常见事件。我们检查并发现了口腔鳞状细胞癌 (SCC) 8p (8p12、8p22) 上两个常见的缺失区域。还评估了定位于8p22的候选肿瘤抑制基因FEZ1/LZTS1(FEZ1)基因的可能参与。在这里，我们分析了 FEZ1 改变是否在口腔 SCC 的发生和进展中发挥作用。在本研究中，我们通过逆转录 PCR (RT-PCR) 检测了 31 个原代口腔 SCC 和 8 个 SCC 衍生细胞系中的 FEZ1 表达。 35% 的肿瘤（31 个中的 11 个）和 100% 的细胞系（8 个中的 8 个）显示 mRNA 基因表达缺失或减少。此外，为了研究沉默机制，用5-氮杂-2'-脱氧胞苷培养细胞，所有细胞系均显示出去甲基化剂的恢复。这些发现表明 FEZ1 基因失活可能有助于口腔鳞状细胞癌的发生。

项目成果

Ono K, Uzawa K, Yama M, Watanabe T, Miyakawa A, Yokoe H, Tazawa H: "Expression of FEZ1 gene in oral squamous cell"Oral Oncology (Editors : AK Varma, JLN Roodenburg). 7. 587-594 (2001)

Ono K、Uzawa K、Yama M、Watanabe T、Miyakawa A、Yokoe H、Tazawa H：“口腔鳞状细胞中 FEZ1 基因的表达”口腔肿瘤学（编辑：AK Varma、JLN Roodenburg）。

Ono K, Uzawa K, Yama M, Watanabe T, Miyakawa A, Yokoe H, Tanzawa H.: "Expression of FEZ1 gene in oral squamous cell"Oral Oncology (Editors : AK Varma, JLN Roodenburg). 7. 587-594 (2001)

Ono K、Uzawa K、Yama M、Watanabe T、Miyakawa A、Yokoe H、Tanzawa H.：“口腔鳞状细胞中 FEZ1 基因的表达”口腔肿瘤学（编辑：AK Varma、JLN Roodenburg）。

Ono K, Uzawa K, Yama M, Watanabe T,Myakawa A, Aisaki K, Yokoe H,Tanzawa H.: "Expression of FEZ1 gene in oral squamous cell carcinoma"Oral Oncology, Valma & Roodenburg edit. 7. 587-594

Ono K、Uzawa K、Yama M、Watanabe T、Myakawa A、Aisaki K、Yokoe H、Tanzawa H.：“FEZ1 基因在口腔鳞状细胞癌中的表达”口腔肿瘤学，Valma