Tissue-specific expression of a suicide gene for selective killing of neuroblastoma cells using a promoter region of the NCX gene.
The human NCX gene, a homologue of the murine neural crest homeobox (Ncx/Hox11L.1) gene whose expression is restricted to a subset of neural crest-derived tissues, was expressed in human neuroblastoma cells but not in other tumors or fibroblasts. A 4.5-kb genomic fragment in the 5'-flanking region of the NCX gene efficiently transcribed the fused luciferase reporter gene in human neuroblastoma cells but not in non-neuroblastoma cells. Sequential deletion of this regulatory region from the 5' side demonstrated that a 1.7-kb fragment upstream from the start codon retained the preferential promoter activity in neuroblastoma cells. The transcriptional activation by the NCX promoter was stronger than that by the SV40 T antigen promoter in human neuroblastoma cells. Transfection of neuroblastoma cells with the NCX promoter-linked herpes simplex virus-thymidine kinase (HSV-TK) gene increased their sensitivity to ganciclovir. The regulatory region of the NCX gene is thus useful for neuroblastoma-specific suicide gene therapy.
Narita
M
M
Division of Pathology, Chiba Cancer Center Research Institute, Chiba, Japan.
Bahar
R
R
Hatano
M
M
Kang
M M
MM
Tokuhisa
T
T
Goto
S
S
Saisho
H
H
Sakiyama
S
S
Tagawa
M
M
D016923:Cell Death / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D018398:Homeodomain Proteins / Q000235:genetics* / Q000627:therapeutic use; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000473:pathology / Q000628:therapy; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D018398:Homeodomain Proteins; C491534:TLX2 protein, human