Abstract
The long-term success of gene therapy for cancer relies heavily on the development of effective targeting systems. We investigate the possibility of targeted gene therapy using promoter of carcinoembryonic antigen (CEA) gene. By using luciferase reporter gene, we found that CEA promoter exhibit 16 times high activity in CEA-producing lung cancer cells, A549 than in nonproducing cells, Hela. We also constructed a recombinant expression plasmid pCEATK, in which CEA promoter drives the effector gene, thymidine kinase gene of Herpes Simplex Virus (HSVTK). A549 cells transfected with pCEATK became 865 times more sensitive to ganciclovir (GCV) than the control cells. However, Hela cells transfected with this plasmid remained resistant to GCV. These data indicate the potential for targeted gene therapy using the CEA promoter against CEA-producing tumor cells, such as lung cancer cells.
Similar content being viewed by others
References
Marcia Barinaga. From bench top to bedside[J].Science, 1997,278: 1036–1039.
Thompson J, Grunert F, Zimmermann W. Carcinoembryonic antigen gene family: molecular biology and clinical perspectives[J].J Clin Lab Anal, 1991,5: 344–366.
Schrewe H, Thompson J, Bona M,et al. Cloning of the comlete gene for carcinoembryonic antigen: analysis of its promoter indicates a region conveying cell type-specific expression[J].Mol Cell Biol, 1990,10: 2738–2748.
Matthews T, Boehme R. Antiviral activity and mechanism of action of ganciclovir[J].Rev Infect Dis, 1988,10: S490-S494.
Mullen C A, Metabolic suicide genes in gene therapy. Pharmac[J].Ther, 1994,63: 199–207.
Martin L A, Lemoine N R. Direct cell killing by suicide genes[J].Cancer and Metastasis Reviews, 1996,15: 301–316.
Alley M C, Scudiero D A, Monks A,et al. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay[J].Cancer Res, 1988,48: 589–601.
Zhang J, Russell S J. Vectors for cancer gene therapy [J].Cancer and Metastasis Reviews, 1996,15: 385–401.
Cossett F L, Morling F J, Takeuchiy,et al. Retroviral retargeting by envelopes expressing an N-terminai binding domain[J].J Virol, 1995,69 (10): 6314–6322.
Wickham T J, Carrion M E, Kovesdi I. Targeting of adenovirus penton base to new receptors through replacement of its RGD motif with other receptor-specific peptide motifs[J].Gene Ther, 1995,2: 750–756.
Culver K W, Ram Z, Wallbridges,et al. In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors[J].Science, 1992,256: 1550–1552.
Bi W L, Parysek L M, Warnick R, Stambrook P J. IN vitro evidence that metabolic cooperation in responsible for the bystander effect observed with HSVTK retroviral gene therapy[J].Hum Gene Ther, 1993,4: 725–732.
Vile R G, Nelson J A, Castleden S,et al. Systemic gene therapy of murine melanoma using tissue specific expression of the HSVTK gene involves an immune component[J].Cancer Res earch, 1994,54: 6223–6234.
Paul S, Dummer S. Topics in clinical pharmacology: ganciclovir[J].Am J Med Sci, 1992,304: 272–277.
Author information
Authors and Affiliations
Additional information
Foundation item: Supported by the National Natural Science Foundation of China Natural Science Foundation of Hubei Province
Biography: XIAO Geng-fu(1966-), male, phD graduate candidate, Lecturer.
Rights and permissions
About this article
Cite this article
Geng-fu, X., Yi-peng, Q., Xuan-hong, C. et al. HSVTK gene therapy for carcinoembryonic antigen-producing human lung cancer cells. Wuhan Univ. J. Nat. Sci. 4, 367–371 (1999). https://doi.org/10.1007/BF02842375
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02842375