1. ¹Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
2. ²Departmentof Biomathematics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
3. ³Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
4. ⁴Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
5. ⁵Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA

Correspondence: Louis L Pisters, Department of Urology, Box 446, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. E-mail: lpisters@mdanderson.org

^aCJR and MT contributed equally to this study.

^bCurrent address: Department of Urology, Nara Medical School, Kashihara, Nara 634-8521, Japan.

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

^dVukar-Lopez F, Rosser CJ, DeLacerda J, Grossman HB, Pisters L, Reyes A. unpublished data.

Received 14 May 2003; Published online 6 February 2004.

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.