To more accurately determine the tissue-specific expression of the target gene in prostate cancer cells, we introduced the enhancer element (–4,777 to –3,934; PSAR) and the promoter region (PSAP) of the prostate-specific antigen (PSA) gene. Furthermore, to elucidate the advantages of using liposomes as a gene carrier, we screened more than 20 liposome preparations in this study. The 5′ upstream region of PSA gene (PSARPSAP) was conjugated to either the chloramphenicol acetyltransferase (CAT) gene or herpes simplex virus thymidine kinase (TK) gene, and the transfection of these plasmids was carried out using cationic liposomes, DMRIE-C (Gibco) or LipoTAXI (Stratagene). The expression of CAT activity was clearly observed when PSARPSAP-CAT plasmid was transfected into PSA-positive LNCaP cells, whereas no CAT activity was detected in PSA-negative DU145 cells or bladder carcinoma T24 cells. The CAT activity increased after the addition of testosterone. We then evaluated the therapeutic effect of the PSARPSAP-TK plasmid in vitro. When PSARPSAP-TK plasmid was transfected and ganciclovir was added to the medium, the growth of LNCaP cells was inhibited, while no growth inhibition was observed in DU145 cells. Furthermore, this inhibitory effect was observable even when the cells were cultured in a medium supplemented with dialyzed fetal bovine serum. These results suggest that the liposome-mediated transfection of PSARPSAP-TK appears to be a potentially effective approach for selecting the optimal treatment for tumor cells producing PSA even with the low androgen levels seen in patients treated by anti-androgen therapy.

Keywords:
Gene therapy, Prostate-specific antigen promoter/enhancer, Prostate cancer, Herpes simplex virus-thymidine kinase/ganciclovir, Liposome
This content is only available via PDF.
© 2001 S. Karger AG, Basel
2001
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.