Reduction of 9-nitrocamptothecin-triggered apoptosis in DU-145 human prostate cancer cells by ectopic expression of 14-3-3ζ

  • Authors:
    • Devasis Chatterjee
    • Melissa Goldman
    • Corey D. Braastad
    • James Darnowski
    • James H. Wyche
    • Panayotis Pantazis
    • Lee Goodglick
  • View Affiliations

  • Published online on: August 1, 2004     https://doi.org/10.3892/ijo.25.2.503
  • Pages: 503-509
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Abstract

A promising family of anticancer agents, the camptothecins, is noted for their ability to induce apoptosis specifically in malignant cells. However, a major obstacle for successful cancer treatment by these and other chemotherapeutic agents is the intrinsic or acquired resistance to drug treatment. Resistance to 9NC6, a camptothecin derivative, has been modeled in vitro using a human prostate cancer cell line. To elucidate the mechanism for acquired 9NC resistance, we have used a subtractive cloning approach to identify genes whose altered expression level is reflective of 9NC resistance or susceptibility. Differential gene expression was compared between wild-type human prostate cancer cell line, DU-145, and a 9NC-resistant subline, RC1. Results were confirmed by Northern and Western blot analyses. In this report, we focus on one gene, 14-3-3ζ. An expression vector of a full-length myc-epitope-tagged 14-3-3ζ cDNA was constructed and used for transfection into DU-145 cells. We consistently observed that 14-3-3ζ message and protein levels were dramatically increased in 9NC resistant cells. The expression levels of other 14-3-3 family members were unaffected. Strikingly, ectopic overexpression of 14-3-3ζ in wild-type 9NC-susceptible prostate cancer cells decreased 9NC-induced apoptosis. Our results suggest a novel direct or indirect role of 14-3-3ζ in mediating resistance of DU-145 cells to the topoisomerase I inhibitor, 9NC. We are currently exploring whether this represents a more general pathway for drug resistance as well.

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August 2004
Volume 25 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Chatterjee D, Goldman M, Braastad CD, Darnowski J, Wyche JH, Pantazis P and Goodglick L: Reduction of 9-nitrocamptothecin-triggered apoptosis in DU-145 human prostate cancer cells by ectopic expression of 14-3-3ζ. Int J Oncol 25: 503-509, 2004
APA
Chatterjee, D., Goldman, M., Braastad, C.D., Darnowski, J., Wyche, J.H., Pantazis, P., & Goodglick, L. (2004). Reduction of 9-nitrocamptothecin-triggered apoptosis in DU-145 human prostate cancer cells by ectopic expression of 14-3-3ζ. International Journal of Oncology, 25, 503-509. https://doi.org/10.3892/ijo.25.2.503
MLA
Chatterjee, D., Goldman, M., Braastad, C. D., Darnowski, J., Wyche, J. H., Pantazis, P., Goodglick, L."Reduction of 9-nitrocamptothecin-triggered apoptosis in DU-145 human prostate cancer cells by ectopic expression of 14-3-3ζ". International Journal of Oncology 25.2 (2004): 503-509.
Chicago
Chatterjee, D., Goldman, M., Braastad, C. D., Darnowski, J., Wyche, J. H., Pantazis, P., Goodglick, L."Reduction of 9-nitrocamptothecin-triggered apoptosis in DU-145 human prostate cancer cells by ectopic expression of 14-3-3ζ". International Journal of Oncology 25, no. 2 (2004): 503-509. https://doi.org/10.3892/ijo.25.2.503