Gene therapy for carcinoembryonic antigen-producing human lung cancer cells by cell type-specific expression of herpes simplex virus thymidine kinase gene.
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.
Osaki
T
T
Department of Medicine III, Osaka University Medical School, Japan.
Tanio
Y
Y
Tachibana
I
I
Hosoe
S
S
Kumagai
T
T
Kawase
I
I
Oikawa
S
S
Kishimoto
T
T
D000230:Adenocarcinoma / Q000378:metabolism / Q000628:therapy*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000628:therapy*; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D005814:Genes, Viral; D015316:Genetic Therapy / Q000379:methods*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000628:therapy*; D008969:Molecular Sequence Data; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics*; D013937:Thymidine Kinase / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000378:metabolism / Q000628:therapy
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D012333:RNA, Messenger; D013937:Thymidine Kinase; D015774:Ganciclovir