Analysis of characterization of a GC factor in malignant brain tumor and its application to the gene therapy

恶性脑肿瘤GC因子特征分析及其在基因治疗中的应用

• 批准号: 09470296
• 负责人: KURISU Kaoru
• 金额: $ 4.29万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470296/
• 关键词: GC factor; malignant glioma; EGFR; adenovirus; cell cycle; NBS1; telomerase; GC-Factor; 抗癌剤; *剤感受性; アデノウィルス; GC factor; アデノウイルスベクター; 細胞増殖抑制; GCfactor; 遺伝子導入

GC factor (GCF) is a human transcriptional regulator that binds to specific GC-rich sequences in the certain genes promoter and represses its transcription. Malignant glioma express multiautocrine loops of growth factor/receptor, especially overexpress the epidermal growth factor receptor (EGFR). We investigated the expression of the EGFR in glioma cell lines. By the use of GCF transfection, we examined whether GCF represses the expression of growth factors and receptors and cause growth inhibition of glioma cells. The transfection of GCF expression vector into glioma cell line (U251-MG) decreased the protein level of EGFR and insulin-like growth factor-II (IGF-II). We also examined the effect of GCF gene transfer on the chemosenstivity to ACNU, CDDP and VCR. The slight increase of sensitivity to ACNU. CDDP and VCR was found. We developed a recomblnant adenovirus expressing GCF gene (AxCA-GCF) by COS-TPC method. We are investigating the growth inhibition of glioma by infection of AxCA-GCF and in vitro and in vivo.Also, we investigated the molecular changes of p16 gene, NBS1, telomerase activity in human gliomas and malignant lymphoma. And we studied p16 gene transfection effects on growth of glioma cells and senstivity of cells to ACNU, CDDP and AZC.

GC因子（GCF）是一种人类转录调节因子，它结合到某些基因启动子中特定的富含GC的序列并抑制其转录。恶性胶质瘤表达生长因子/受体的多自分泌环，尤其是表皮生长因子受体（EGFR）的过表达。我们研究了EGFR在胶质瘤细胞系中的表达。通过转染GCF，我们检测了GCF是否抑制生长因子和受体的表达，从而导致胶质瘤细胞的生长抑制。GCF表达载体转染胶质瘤细胞系（U251-MG）后，EGFR和胰岛素样生长因子- ii （IGF-II）蛋白水平降低。我们还研究了GCF基因转移对ACNU、CDDP和VCR的化学敏感性的影响。对ACNU的敏感性略有增加。发现CDDP和VCR。我们采用COS-TPC法构建了表达GCF基因的重组腺病毒（AxCA-GCF）。我们正在体外和体内研究感染AxCA-GCF对胶质瘤生长的抑制作用。此外，我们还研究了p16基因、NBS1、端粒酶活性在胶质瘤和恶性淋巴瘤中的变化。研究p16基因转染对胶质瘤细胞生长及细胞对ACNU、CDDP、AZC的敏感性的影响。

项目成果

Harada Kunyu: "Telomerase acitivity in central nervous cystem malignant lymphoma"Cancer. 86. 1050-1055 (1999)

Harada Kunyu：“中枢神经囊肿恶性淋巴瘤中的端粒酶活性”癌症。

Kaoru Kurisu: "Induction and maintenance therapy for high grade glioma of cerepral hemisphere using ACNC.platium,CSF"Proceedings of 11th ICNS. 411-415 (1997)

Kaoru Kurisu：“使用 ACNC.platium、CSF 对大脑半球高级神经胶质瘤进行诱导和维持治疗”第 11 届 ICNS 会议记录。

Seiji Hama: "Absence of mutations in the NBSI gene in B-cell malignant lymphoma patients"Anticancer research. (2000)

Seiji Hama：“B细胞恶性淋巴瘤患者的NBSI基因不存在突变”抗癌研究。

Hiroyuki Yoshioka: "Peritumoval Brain Edema Associated with Mewingioima." CANCER. 85(4). 936-944 (1999)

Hiroyuki Yoshioka：“与 Mewingioima 相关的瘤周脑水肿。”

Kunyu Harada: "Telomerase activity in human brain tumors"Proceedings of 11th ICNS. 1787-1791 (1997)

Kunyu Harada：“人类脑肿瘤中的端粒酶活性”第 11 届 ICNS 会议记录。