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

Cancer Gene Ther. 2004 Apr;11(4):273-9. doi: 10.1038/sj.cgt.7700673.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics*
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Down-Regulation / genetics
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Genetic Therapy / methods
  • Genetic Vectors / genetics
  • Humans
  • Immunochemistry
  • Male
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases / genetics*
  • Phosphoric Monoester Hydrolases / metabolism
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / radiotherapy*
  • Prostatic Neoplasms / therapy
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Radiation Tolerance
  • Transfection
  • Transgenes / genetics
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism


  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Proteins
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • PTEN protein, human