Miyauchi M, Shimada H, Kadomatsu K, Muramatsu T, Matsubara S, Ikematsu S, Takenaga K, Asano T, Ochiai T, Sakiyama S, Tagawa M
Division of Pathology, Chiba University School of Medicine.
Jpn J Cancer Res. 1999 Apr;90(4):469-75. doi: 10.1111/j.1349-7006.1999.tb00771.x.
We have examined the expression of midkine (MK), a neurotrophic factor with heparin-binding activity, in human esophageal cancer cells. Seven esophageal cell lines tested expressed the transcript and 8 out of 14 human esophageal tumor specimens were positively stained with anti-MK antibody, while surrounding normal esophageal tissues in these specimens were not stained. The 5'-flanking, 2.3 kb genomic region of the MK gene was shown to drive the transcription of a reporter gene in the esophageal cell lines in a cis acting manner. Forced expression in esophageal cancer cells of herpes simplex virus-thymidine kinase gene mediated by the flanking region of the MK gene conferred sensitivity to a prodrug, ganciclovir. The 5'-upstream region of the MK gene thus possesses putative promoter activity which can be used for suicide gene-based gene therapy for esophageal cancer.
我们检测了中期因子（MK）在人食管癌细胞中的表达，MK是一种具有肝素结合活性的神经营养因子。所检测的7种食管细胞系均表达该转录本，14例人食管肿瘤标本中有8例被抗MK抗体阳性染色，而这些标本周围的正常食管组织未被染色。MK基因2.3kb的5'侧翼基因组区域以顺式作用方式驱动食管细胞系中报告基因的转录。由MK基因侧翼区域介导的单纯疱疹病毒胸苷激酶基因在食管癌细胞中的强制表达赋予了对前体药物更昔洛韦的敏感性。因此，MK基因的5'上游区域具有推定的启动子活性，可用于基于自杀基因的食管癌基因治疗。
