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Adenoviral-mediated PTEN transgene expression sensitizes Bcl-2-expressing prostate cancer cells to radiation

Cancer Gene Therapy volume 11, pages 273–279 (2004)Cite this article

Abstract

Bcl-2 is associated with resistance to radiotherapy in prostate cancer. It was recently demonstrated that transduction of LNCaP prostate cells with the PTEN gene resulted in Bcl-2 downregulation. We hypothesized that forced expression of PTEN in prostate cancer cells would sensitize cells to radiation, downregulate Bcl-2 expression, and potentiate the G2M block induced by radiation. Four cell lines — PC-3-Bcl-2 (Bcl-2 overexpression, deleted PTEN), PC-3-Neo (wild-type Bcl-2, deleted PTEN), LNCaP (Bcl-2 overexpression, deleted PTEN), and DU-145 (wild-type Bcl-2 and PTEN) — were transduced with a recombinant adenovirus-5 vector expressing the human wild-type PTEN cDNA under the control of a human cytomegalovirus promoter (Ad-MMAC). After correction for the effect of Ad-MMAC on plating efficiency, Ad-MMAC treatment reduced the surviving fractions after 2 Gy as follows: PC-3-Bcl-2, from 60.5 to 3.6%; PC-3-Neo, no reduction; LNCaP, from 29.6 to 16.3%; and DU-145, from 32.7 to 25.7%. PTEN expression was associated with the downregulation of Bcl-2 expression in PC-3-Bcl-2 and LNCaP cell lines. Ad-MMAC plus radiotherapy potentiated the G2M block seen with radiotherapy alone only in PC-3-Bcl-2 cells. These findings suggest that overexpression of Bcl-2 result in radioresistance and inability of radiation to cause its typical G2M cell-cycle arrest.

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Acknowledgements

Stephanie Deming and Dr Kwai Wa Cheng for his careful review of the manuscript. This work was supported by American Foundation of Urologic Disease grant and National Cancer Institute Grants CA56973 and CA16672.

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Author notes

  1. Motoyoshi Tanaka

    Present address: Department of Urology, Nara Medical School, Kashihara, Nara, 634-8521, Japan

  2. Charles J Rosser

    Present address: Division of Urology, University of Florida Shands, 555 West 8th St., Jacksoulle, FL, 32207

  3. Charles J Rosser: CJR and MT contributed equally to this study.

  4. Charles J Rosser: Vukar-Lopez F, Rosser CJ, DeLacerda J, Grossman HB, Pisters L, Reyes A. unpublished data.

Authors and Affiliations

  1. Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USA

    Charles J Rosser, Motoyoshi Tanaka, Louis L Pisters, Noriyoshi Tanaka, David C Hoover & H Barton Grossman

  2. Departmentof Biomathematics, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USA

    Lawrence B Levy

  3. Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USA

    Timothy J McDonnell

  4. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USA

    Deborah A Kuban

  5. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USA

    Raymond E Meyn

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  1. Charles J Rosser
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Correspondence to Louis L Pisters.

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Rosser, C., Tanaka, M., Pisters, L. et al. Adenoviral-mediated PTEN transgene expression sensitizes Bcl-2-expressing prostate cancer cells to radiation. Cancer Gene Ther 11, 273–279 (2004). https://doi.org/10.1038/sj.cgt.7700673

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