Adenoviral-E2F-1 radiosensitizes p53wild-type and p53 null human prostate cancer cells

Khanh H. Nguyen, Paul Hachem, Li Yan Khor, Naji Salem, Kelly K. Hunt, Peter R. Calkins, Alan Pollack

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Purpose: E2F-1 is a transcription factor that enhances the radiosensitivity of various cell lines by inducing apoptosis. However, there are conflicting data concerning whether this enhancement is mediated via p53 dependent pathways. Additionally, the role of E2F-1 in the response of human prostate cancer to radiation has not been well characterized. In this study, we investigated the effect of Adenoviral-E2F-1 (Ad-E2F-1) on the radiosensitivity of p53 wild-type (LNCaP) and p53null (PC3) prostate cancer cell lines. Methods and Materials: LNCaP and PC3 cells were transduced with Ad-E2F-1, Adenoviral-Luciferase (Ad-Luc) control vector, or Adenoviral-p53 (Ad-p53). Expression of E2F-1 and p53 was examined by Western blot analysis. Annexin V and caspase 3 + 7 assays were performed to estimate the levels of apoptosis. Clonogenic survival assays were used to determine overall cell death. Statistical significance was determined by analysis of variance, using the Bonferroni method to correct for multiple comparisons. Results: Western blot analysis confirmed the efficacy of transductions with Ad-E2F-1 and Ad-p53. Ad-E2F-1 transduction significantly enhanced apoptosis and decreased clonogenic survival in both cell lines. These effects were compounded by the addition of RT. Although E2F-1-mediated radiosensitization was independent of p53 status, this effect was more pronounced in p53wild-type LNCaP cells. When PC3 cells were treated with Ad-p53 in combination with RT and Ad-E2F-1, there was at least an additive reduction in clonogenic survival. Conclusions: Our results suggest that Ad-E2F-1 significantly enhances the response of p53 wild-type and p53null prostate cancer cells to radiation therapy, although radiosensitization is more pronounced in the presence of p53. Ad-E2F-1 may be a useful adjunct to radiation therapy in the treatment of prostate cancer.

Original languageEnglish
Pages (from-to)238-246
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume63
Issue number1
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

Fingerprint

Prostatic Neoplasms
apoptosis
cancer
cultured cells
Radiation Tolerance
radiation tolerance
Apoptosis
Cell Line
Survival
radiation therapy
Radiotherapy
Western Blotting
cells
directional control
Caspase 7
analysis of variance
Annexin A5
Luciferases
death
Caspase 3

Keywords

  • Adenoviral gene therapy
  • Apoptosis
  • E2F-1
  • Prostate cancer
  • Radiation

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Adenoviral-E2F-1 radiosensitizes p53wild-type and p53 null human prostate cancer cells. / Nguyen, Khanh H.; Hachem, Paul; Khor, Li Yan; Salem, Naji; Hunt, Kelly K.; Calkins, Peter R.; Pollack, Alan.

In: International Journal of Radiation Oncology Biology Physics, Vol. 63, No. 1, 01.09.2005, p. 238-246.

Research output: Contribution to journalArticle

Nguyen, Khanh H. ; Hachem, Paul ; Khor, Li Yan ; Salem, Naji ; Hunt, Kelly K. ; Calkins, Peter R. ; Pollack, Alan. / Adenoviral-E2F-1 radiosensitizes p53wild-type and p53 null human prostate cancer cells. In: International Journal of Radiation Oncology Biology Physics. 2005 ; Vol. 63, No. 1. pp. 238-246.
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T1 - Adenoviral-E2F-1 radiosensitizes p53wild-type and p53 null human prostate cancer cells

AU - Nguyen, Khanh H.

AU - Hachem, Paul

AU - Khor, Li Yan

AU - Salem, Naji

AU - Hunt, Kelly K.

AU - Calkins, Peter R.

AU - Pollack, Alan

PY - 2005/9/1

Y1 - 2005/9/1

N2 - Purpose: E2F-1 is a transcription factor that enhances the radiosensitivity of various cell lines by inducing apoptosis. However, there are conflicting data concerning whether this enhancement is mediated via p53 dependent pathways. Additionally, the role of E2F-1 in the response of human prostate cancer to radiation has not been well characterized. In this study, we investigated the effect of Adenoviral-E2F-1 (Ad-E2F-1) on the radiosensitivity of p53 wild-type (LNCaP) and p53null (PC3) prostate cancer cell lines. Methods and Materials: LNCaP and PC3 cells were transduced with Ad-E2F-1, Adenoviral-Luciferase (Ad-Luc) control vector, or Adenoviral-p53 (Ad-p53). Expression of E2F-1 and p53 was examined by Western blot analysis. Annexin V and caspase 3 + 7 assays were performed to estimate the levels of apoptosis. Clonogenic survival assays were used to determine overall cell death. Statistical significance was determined by analysis of variance, using the Bonferroni method to correct for multiple comparisons. Results: Western blot analysis confirmed the efficacy of transductions with Ad-E2F-1 and Ad-p53. Ad-E2F-1 transduction significantly enhanced apoptosis and decreased clonogenic survival in both cell lines. These effects were compounded by the addition of RT. Although E2F-1-mediated radiosensitization was independent of p53 status, this effect was more pronounced in p53wild-type LNCaP cells. When PC3 cells were treated with Ad-p53 in combination with RT and Ad-E2F-1, there was at least an additive reduction in clonogenic survival. Conclusions: Our results suggest that Ad-E2F-1 significantly enhances the response of p53 wild-type and p53null prostate cancer cells to radiation therapy, although radiosensitization is more pronounced in the presence of p53. Ad-E2F-1 may be a useful adjunct to radiation therapy in the treatment of prostate cancer.

AB - Purpose: E2F-1 is a transcription factor that enhances the radiosensitivity of various cell lines by inducing apoptosis. However, there are conflicting data concerning whether this enhancement is mediated via p53 dependent pathways. Additionally, the role of E2F-1 in the response of human prostate cancer to radiation has not been well characterized. In this study, we investigated the effect of Adenoviral-E2F-1 (Ad-E2F-1) on the radiosensitivity of p53 wild-type (LNCaP) and p53null (PC3) prostate cancer cell lines. Methods and Materials: LNCaP and PC3 cells were transduced with Ad-E2F-1, Adenoviral-Luciferase (Ad-Luc) control vector, or Adenoviral-p53 (Ad-p53). Expression of E2F-1 and p53 was examined by Western blot analysis. Annexin V and caspase 3 + 7 assays were performed to estimate the levels of apoptosis. Clonogenic survival assays were used to determine overall cell death. Statistical significance was determined by analysis of variance, using the Bonferroni method to correct for multiple comparisons. Results: Western blot analysis confirmed the efficacy of transductions with Ad-E2F-1 and Ad-p53. Ad-E2F-1 transduction significantly enhanced apoptosis and decreased clonogenic survival in both cell lines. These effects were compounded by the addition of RT. Although E2F-1-mediated radiosensitization was independent of p53 status, this effect was more pronounced in p53wild-type LNCaP cells. When PC3 cells were treated with Ad-p53 in combination with RT and Ad-E2F-1, there was at least an additive reduction in clonogenic survival. Conclusions: Our results suggest that Ad-E2F-1 significantly enhances the response of p53 wild-type and p53null prostate cancer cells to radiation therapy, although radiosensitization is more pronounced in the presence of p53. Ad-E2F-1 may be a useful adjunct to radiation therapy in the treatment of prostate cancer.

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