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Eradication of Myc-overexpressing Small Cell Lung Cancer Cells Transfected with Herpes Simplex Virus Thymidine Kinase Gene Containing Myc-Max Response Elements¹

Department of Medicine III, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565 [T. Ku., Y. T., T. O., S. H., I. T., K. U., T. Kij., T. Kis.], and Department of Medicine IV, The Center for Adult Disease, Osaka, 3-3 Nakamichi 1-chome, Higashinari-ku, Osaka 537 [T. H.], Japan

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.

¹ This work was supported in part by Grants-in-Aid from the Ministry of Education, Science, and Culture, Japan, and from the Ministry of Health and Welfare, Japan.

² To whom requests for reprints should be addressed.

Received 8/14/95. Accepted 11/13/95.

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