Osaki T, Tanio Y, Tachibana I, Hosoe S, Kumagai T, Kawase I, Oikawa S, Kishimoto T
Department of Medicine III, Osaka University Medical School, Japan.
Cancer Res. 1994 Oct 15;54(20):5258-61.
A carcinoembryonic antigen (CEA)-producing human lung cancer cell line (A549), a nonproducing human lung cancer cell line (CADO-LC9), and a human uterine cervical cancer (HeLa) were transfected with the herpes simplex virus thymidine kinase (HSV-TK) gene regulated by 445 nucleotides upstream from the translational start of CEA gene. Fifty % growth inhibitory concentration of ganciclovir (GCV) was 0.57 micron for HSV-TK-transfected A549; relative sensitivity to GCV was more than 1000 times higher compared to the 50% growth inhibitory concentration of the parental cell line. Both CADO-LC9 and HeLa transfected with HSV-TK were still resistant to GCV. There was no difference in either morphology or doubling time between HSV-TK-transfected and parental clones. Injections (i.p.) of GCV resulted in significant regression of HSV-TK-transfected A549 tumors in nude mice. These data show the possibility of gene therapy using the cell type-specific promoter of CEA gene against CEA-producing adenocarcinoma of the lung.
用受癌胚抗原（CEA）基因翻译起始上游445个核苷酸调控的单纯疱疹病毒胸苷激酶（HSV-TK）基因转染产生CEA的人肺癌细胞系（A549）、不产生CEA的人肺癌细胞系（CADO-LC9）和人子宫颈癌细胞（HeLa）。对于转染了HSV-TK的A549细胞，更昔洛韦（GCV）的50%生长抑制浓度为0.57微米；与亲代细胞系的50%生长抑制浓度相比，其对GCV的相对敏感性高出1000倍以上。转染了HSV-TK的CADO-LC9和HeLa对GCV仍有抗性。转染了HSV-TK的克隆和亲代克隆在形态或倍增时间上均无差异。腹腔注射GCV可使转染了HSV-TK的A549肿瘤在裸鼠体内显著消退。这些数据表明，利用CEA基因的细胞类型特异性启动子对产生CEA的肺腺癌进行基因治疗具有可能性。
