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.
Miyauchi
M
M
Division of Pathology, Chiba University School of Medicine.
Shimada
H
H
Kadomatsu
K
K
Muramatsu
T
T
Matsubara
S
S
Ikematsu
S
S
Takenaga
K
K
Asano
T
T
Ochiai
T
T
Sakiyama
S
S
Tagawa
M
M
D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D002352:Carrier Proteins / Q000235:genetics*; D016207:Cytokines; D004938:Esophageal Neoplasms / Q000628:therapy*; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000078792:Midkine; D009363:Neoplasm Proteins / Q000235:genetics*; D009414:Nerve Growth Factors / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D002352:Carrier Proteins; D016207:Cytokines; D009363:Neoplasm Proteins; D009414:Nerve Growth Factors; D000078792:Midkine; D015774:Ganciclovir