This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kumagai, T. Articles by Kishimoto, T. Search for Related Content PubMed PubMed Citation Articles by Kumagai, T. Articles by Kishimoto, T.

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.

This article has been cited by other articles:

				H. Wang, D. I. Hammoudeh, A. V. Follis, B. E. Reese, J. S. Lazo, S. J. Metallo, and E. V. Prochownik Improved low molecular weight Myc-Max inhibitors Mol. Cancer Ther., September 1, 2007; 6(9): 2399 - 2408. [Abstract] [Full Text] [PDF]

				L. Barzon, M. Boscaro, and G. Palu Endocrine Aspects of Cancer Gene Therapy Endocr. Rev., February 1, 2004; 25(1): 1 - 44. [Abstract] [Full Text] [PDF]

				C. Moon, Y. Oh, and J. A. Roth Current Status of Gene Therapy for Lung Cancer and Head and Neck Cancer Clin. Cancer Res., November 1, 2003; 9(14): 5055 - 5067. [Abstract] [Full Text] [PDF]

				R. V. Iyengar, C. A. Pawlik, E. J. Krull, D. A. Phelps, R. A. Burger, L. C. Harris, P. M. Potter, and M. K. Danks Use of a Modified Ornithine Decarboxylase Promoter to Achieve Efficient c-MYC- or N-MYC-regulated Protein Expression Cancer Res., April 1, 2001; 61(7): 3045 - 3052. [Abstract] [Full Text]

				T. Kijima, T. Osaki, K. Nishino, T. Kumagai, T. Funakoshi, H. Goto, I. Tachibana, Y. Tanio, and T. Kishimoto Application of the Cre Recombinase/loxP System Further Enhances Antitumor Effects in Cell Type-specific Gene Therapy against Carcinoembryonic Antigen-producing Cancer Cancer Res., October 1, 1999; 59(19): 4906 - 4911. [Abstract] [Full Text] [PDF]

				M. K. Danks, C. L. Morton, E. J. Krull, P. J. Cheshire, L. B. Richmond, C. W. Naeve, C. A. Pawlik, P. J. Houghton, and P. M. Potter Comparison of Activation of CPT-11 by Rabbit and Human Carboxylesterases for Use in Enzyme/Prodrug Therapy Clin. Cancer Res., April 1, 1999; 5(4): 917 - 924. [Abstract] [Full Text] [PDF]