Frequent Expression of Midkine Gene in Esophageal Cancer Suggests a Potential Usage of Its Promoter for Suicide Gene Therapy

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.