Eradication of Myc-overexpressing small cell lung cancer cells transfected with herpes simplex virus thymidine kinase gene containing Myc-Max response elements

Herpes simplex virus thymidine kinase (HSV-TK) gene was ligated with four repeats of the Myc-Max response elements (a core nucleotide sequence CACGTG), and its utility for gene therapy was examined by the treatment of either c-, L- or N-myc-overexpressing the small cell lung cancer (SCLC) cell line...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1996-01, Vol.56 (2), p.354-358
Main Authors: KUMAGAI, T, TANIO, Y, OSAKI, T, HOSOE, S, TACHIBANA, I, UENO, K, KIJIMA, T, HORAI, T, KISHIMOTO, T
Format: Article
Language:English
Subjects:
Antimetabolites, Antineoplastic - pharmacology
Antineoplastic agents
Base Sequence
Biological and medical sciences
Carcinoma, Small Cell - enzymology
Carcinoma, Small Cell - genetics
Carcinoma, Small Cell - therapy
Cell Division - drug effects
Cell Division - physiology
Ganciclovir - pharmacology
Gene Expression
General aspects
Genes, myc
Genetic Therapy
Humans
Lung Neoplasms - enzymology
Lung Neoplasms - genetics
Lung Neoplasms - therapy
Medical sciences
Molecular Sequence Data
Pharmacology. Drug treatments
Promoter Regions, Genetic
Simplexvirus - enzymology
Simplexvirus - genetics
Thymidine Kinase - biosynthesis
Thymidine Kinase - genetics
Transfection
Tumor Cells, Cultured
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Summary:Herpes simplex virus thymidine kinase (HSV-TK) gene was ligated with four repeats of the Myc-Max response elements (a core nucleotide sequence CACGTG), and its utility for gene therapy was examined by the treatment of either c-, L- or N-myc-overexpressing the small cell lung cancer (SCLC) cell line with ganciclovir (GCV). The chloramphenicol acetyltransferase assay demonstrated that the overexpression of any myc genes activated transcription from the CAT gene depending on the Myc-Max binding sites. The transduction of the HSV-TK gene ligated with the CACGTG core rendered all three SCLC lines to be more sensitive to GCV than parental ones in vitro. In addition, the growth of c- or L-myc-overexpressing SCLC cells containing the hybrid HSV-TK gene were significantly suppressed by GCV in vivo. When parental SCLC cells were mixed with HSV-TK-expressing tumor cells at a ratio of 1:3, GCV treatment inhibited tumor growth by 90% compared with parental cells only, indicating the existence of the "bystander effect." These data suggest that the CACGTG-driven HSV-TK gene may be useful for the treatment of SCLC overexpressing any type of myc family oncogenes.
ISSN:0008-5472
1538-7445